subject:(MAPK)

Texas A&M University

1. Jayant Kumar Ojha, Nikita. Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa.

Degree: 2016, Texas A&M University

URL: http://hdl.handle.net/1969.1/157101

► Circadian regulation of Mitogen Activated Protein Kinase (MAPK) pathways provides a priming mechanism to allow organisms to anticipate daily environmental stresses such as heat, light,… (more)

▼ Circadian regulation of Mitogen Activated Protein Kinase (MAPK) pathways provides a priming mechanism to allow organisms to anticipate daily environmental stresses such as heat, light, desiccation and osmotic stress. In Neurospora crassa, the OS MAPK pathway, which is homologous to the p38 MAPK pathway in mammals and the Hog pathway in yeast, is important for adaptation to osmotic stress. The OS pathway consists of two modules: a sensory phosphorelay and a downstream MAPK module. Previous work in our lab demonstrated that under constant environmental conditions, the circadian clock controls daily activation of the MAPK OS-2, through direct transcriptional regulation of the MAPKKK, OS-4. Although this signaling is necessary for rhythmic activation of OS-2, it is not known if it is sufficient for robustness in the amplitude of the rhythms. An upstream phosphorelay, consisting of a sensor histidine kinase (OS-1), a phosphotransferase (HPT-1) and a response regulator (RRG-1), is required for acute stress signaling to the MAPK cascade to activate OS-2. We discovered that the levels of RRG-1 are clock-controlled, suggesting that the phosphorelay functions to regulate rhythms in activation of OS MAPK cascade. To test this idea, I generated constructs with mutations in the phosphorylation site of RRG-1 that will abolish rhythmic activation of the phosphorelay components. These strains will be used to determine if loss of temporal activation of the phosphorelay alters rhythmic accumulation of active OS-2. In addition, transcriptional reporter fusion construct was generated to test if rrg-1 transcription is under the control of the circadian clock. To detect phosphorylation of RRG-1, phos-tag coupled with SDS-PAGE gels was used. This procedure will be utilized in future studies to test if phosphorylation of RRG-1 is rhythmic. Further, two upstream histidine kinases (NCU07221 and NCU00939) were validated as direct targets of the white collar complex (WCC). Tagged versions of these proteins were generated, which will be used in future studies to determine if these histidine kinases accumulate with a circadian rhythm to further understand their role in the clock regulation of the OS MAPK phosphorelay. Advisors/Committee Members: Bell-Pedersen, Deborah (advisor), Hardin, Paul (committee member), Sachs, Matthew (committee member), Ko, Gladys (committee member).

Subjects/Keywords: MAPK; phosphorelay; circadian

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APA (6^th Edition):

Jayant Kumar Ojha, N. (2016). Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/157101

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jayant Kumar Ojha, Nikita. “Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa.” 2016. Thesis, Texas A&M University. Accessed November 20, 2019. http://hdl.handle.net/1969.1/157101.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jayant Kumar Ojha, Nikita. “Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa.” 2016. Web. 20 Nov 2019.

Vancouver:

Jayant Kumar Ojha N. Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa. [Internet] [Thesis]. Texas A&M University; 2016. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/1969.1/157101.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jayant Kumar Ojha N. Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa. [Thesis]. Texas A&M University; 2016. Available from: http://hdl.handle.net/1969.1/157101

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas A&M University

2. Goldsmith, Charles Sidney. Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock.

Degree: 2013, Texas A&M University

URL: http://hdl.handle.net/1969.1/151390

► Mitogen activated protein kinase (MAPK) pathways are conserved biochemical signal transduction pathways in eukaryotic organisms. These signaling pathways demonstrate great versatility in their ability to… (more)

▼ Mitogen activated protein kinase (MAPK) pathways are conserved biochemical signal transduction pathways in eukaryotic organisms. These signaling pathways demonstrate great versatility in their ability to detect various environmental stimuli and direct an appropriate cellular response. The circadian clock is a timekeeping mechanism that temporally coordinates diverse biological functions in an organism with the environment. Thus, it is not surprising that MAPK pathways have been utilized by the circadian clock to regulate many essential functions. Due to the conserved nature of circadian clocks and MAPK signaling pathways in eukaryotes, it is possible to develop hypotheses in simple model organisms, such as the fungus Neurospora, that are relevant to more complex organisms. The OS-2 MAPK pathway in the filamentous fungus Neurospora is rhythmically activated by the circadian clock. In order to generate this rhythmic signal, the circadian oscillator directly regulates the rhythmic transcription of the os-4 MAPKKK and histidine phosphotransferase hpt-1, which are upstream regulators of the OS-2 MAPK. Also, the circadian rhythm in MAPK activation produces a more robust stress response during the time of the day that stress is most likely to be encountered. Based on these data, a model for the clock regulation of MAPK activation is presented, and a biological significance is assigned to the rhythms in this pathway. Informed by these findings in Neurospora, the related p38 MAPK pathway was studied in mammalian cell lines that represent functionally distinct tissues in regards to clock function. A rhythm in p38 MAPK activation was observed in cells derived from the suprachiasmatic nucleus and fibroblasts of a mouse, the master pacemaker and a peripheral tissue, respectively. In cells that lacked a functional circadian oscillator, the rhythm in p38 activation was absent, and overall levels of p38 protein were lower. These data demonstrate a circadian clock-dependent oscillation in p38 activity. These studies provide a basis to understand how the circadian clock generates endogenous rhythms in MAPK signal transduction pathways. Also, the characterization of clock-regulated stress response pathways provides an understanding of the adaptive advantage of the circadian clock. Advisors/Committee Members: Bell-Pedersen, Deborah (advisor), Hardin, Paul E. (committee member), Riley, Bruce (committee member), Wilkinson, Heather (committee member).

Subjects/Keywords: MAPK; circadian; Neurospora; biological clocks

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Goldsmith, C. S. (2013). Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/151390

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Goldsmith, Charles Sidney. “Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock.” 2013. Thesis, Texas A&M University. Accessed November 20, 2019. http://hdl.handle.net/1969.1/151390.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Goldsmith, Charles Sidney. “Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock.” 2013. Web. 20 Nov 2019.

Vancouver:

Goldsmith CS. Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock. [Internet] [Thesis]. Texas A&M University; 2013. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/1969.1/151390.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Goldsmith CS. Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock. [Thesis]. Texas A&M University; 2013. Available from: http://hdl.handle.net/1969.1/151390

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff, Anja Katrin. Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性.

Degree: 博士（医学）, 2013, Nara Medical University / 奈良県立医科大学

URL: http://hdl.handle.net/10564/2670

►

The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). MIA2 expression was observed in 62 (66.7%) of… (more)

Subjects/Keywords: apoptosis; VEGF; integrin; MAPK

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APA (6^th Edition):

Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff, A. K. (2013). Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性. (Thesis). Nara Medical University / 奈良県立医科大学. Retrieved from http://hdl.handle.net/10564/2670

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff, Anja Katrin. “Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性.” 2013. Thesis, Nara Medical University / 奈良県立医科大学. Accessed November 20, 2019. http://hdl.handle.net/10564/2670.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff, Anja Katrin. “Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性.” 2013. Web. 20 Nov 2019.

Vancouver:

Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff AK. Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性. [Internet] [Thesis]. Nara Medical University / 奈良県立医科大学; 2013. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/10564/2670.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kurihara, Miyako; Kirita, Tadaaki; Sasahira, Tomonori; Ohmori, Hitoshi; Matsushima, Sayako; Yamamoto, Kazuhiko; Bosserhoff AK. Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma : 口腔扁平上皮癌におけるmelanoma inhibitory activity 2 (MIA2)の腫瘍促進性. [Thesis]. Nara Medical University / 奈良県立医科大学; 2013. Available from: http://hdl.handle.net/10564/2670

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia State University

4. Farah-Abraham, Rachael M. B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis.

Degree: PhD, Biology, 2011, Georgia State University

URL: https://scholarworks.gsu.edu/biology_diss/98

► B virus (Macacine herpesvirus 1), subfamily Alphaherpesvirinae, causes a fatal, neurovirulent infection in zoonotically infected humans. Macaques (Macaca sp.) serve as the natural host… (more)

▼ B virus (Macacine herpesvirus 1), subfamily Alphaherpesvirinae, causes a fatal, neurovirulent infection in zoonotically infected humans. Macaques (Macaca sp.) serve as the natural host for B virus and they are frequently seropositive for B virus antibodies without showing any overt signs of disease. The global hypothesis of these studies is that B virus, a highly cytopathic virus in macaques, subverts the innate immune responses in the host (macaques) that has co-evolved with it (the virus) differently than it does the foreign host (humans). The foreign host, frequently fails to produce neutralizing antibodies early after infection and this may be due to a dysregulation or inhibition of pathways known to play a role in the innate immune response which directs the adaptive defense responses. Current knowledge is that at least five major signaling pathways can be activated after a pathogen such as B virus enters a host cell (REF). These include the IRF3 pathway, the NFkB pathway, the NFAT pathway, and the MAPK pathway. Early stimulation of one or more of these pathways leads to the induction of the proinflammatory response and subsequent induction of cytokines such as IL6, IL8 and IL10, and apoptosis. Cytokine induction and apoptosis play important roles in host-pathogen interactions, innate defense induction and subsequent adaptive immune responses. Using a primary cell model that is representative of the first target cells of B virus in the natural and foreign host, we investigated one of the key signaling pathways, the MAPK pathway, induced by B virus early after infection (Farah-Abraham and Hilliard, unpublished data). My data suggest that macaque and human cells differ in the induction kinetics of MAPK (JNK and p38) activation. These data reveal differences between foreign and natural host cells in how each controls apoptosis, and demonstrate that inhibition of p38 activation reduced and with high dose inhibition terminated B virus replication in human cells, and played a role in reduction of apoptosis-associated mediators. The importance of each component in the MAPK pathway is investigated with respect to virus replication in macaque and human cells that represent the primary target cells in acute infection. Knowledge of these events provides an understanding of how the innate immune responses can be modulated by B virus to shape the adaptive immune response to limit how the virus replicates and spreads. Further, these data may provide insight into a novel target for the design of new antivirals to inhibit this deadly zoonotic virus. This research will help us understand how the early molecular mechanisms of host-pathogen interactions result in modulation of the innate immune responses and how certain aspects of a normally defensive (protective) host response can be re-directed or modified depending on the nature of the virus:host relationship. Advisors/Committee Members: Julia Hilliard, Richard Dix, Terial Frey.

Subjects/Keywords: B virus; MAPK; Macaque; Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Farah-Abraham, R. M. (2011). B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis. (Doctoral Dissertation). Georgia State University. Retrieved from https://scholarworks.gsu.edu/biology_diss/98

Chicago Manual of Style (16^th Edition):

Farah-Abraham, Rachael M. “B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis.” 2011. Doctoral Dissertation, Georgia State University. Accessed November 20, 2019. https://scholarworks.gsu.edu/biology_diss/98.

MLA Handbook (7^th Edition):

Farah-Abraham, Rachael M. “B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis.” 2011. Web. 20 Nov 2019.

Vancouver:

Farah-Abraham RM. B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis. [Internet] [Doctoral dissertation]. Georgia State University; 2011. [cited 2019 Nov 20]. Available from: https://scholarworks.gsu.edu/biology_diss/98.

Council of Science Editors:

Farah-Abraham RM. B Virus Infection Activates p38 And JNK Pathways Differentially In Cells From Macaque Versus Human Hosts: Exploring Inflammation & Apoptosis. [Doctoral Dissertation]. Georgia State University; 2011. Available from: https://scholarworks.gsu.edu/biology_diss/98

Penn State University

5. Martin, Tony Dewayne. An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading.

Degree: MS, Physiology, 2014, Penn State University

URL: https://etda.libraries.psu.edu/catalog/20079

► ABSTRACT The protein kinase p70S6K1 is a known regulator of cell growth as deletion of its gene results in smaller cell size and consequently reduced… (more)

▼ ABSTRACT The protein kinase p70S6K1 is a known regulator of cell growth as deletion of its gene results in smaller cell size and consequently reduced organ and body sizes. Its activity is modulated through multisite phosphorylation, some of which is mediated by the mechanistic target of rapamycin complex 1 (mTORC1) pathway. The present project was designed to investigate the roles of mTORC1 and that of other signaling pathways in the phosphorylation of p70S6K1 in an animal model of induced hypertrophic growth of skeletal muscle. Within 24 h of male Sprague Dawley rats undergoing unilateral tenotomy to induce chronic functional overloading of the plantaris muscle, phosphorylation of the Thr389 and the Thr421/Ser424 sites on p70S6K1 was significantly elevated compared to a control plantaris from the contralateral leg. To further investigate regulation of phosphorylation of these sites on p70S6K1, a cell culture model system was employed for easier manipulation of signaling pathways. In HEK293E cells deprived of serum for 2.5 h to impair cell growth, treatment with insulin-like-growth factor 1 (IGF-1) for 30 min resulted in a robust stimulation of the phosphorylation of the Thr389 and the Thr421/Ser424 sites on p70S6K1. In this model system, rapamycin, an inhibitor of mTORC1, and TORIN2, an inhibitor of both mTORC1 and mTORC2, each prevented IGF-1-induced stimulated phosphorylation of the Thr389 site on p70S6K1 but not that of the Thr421/Ser424 sites. The JNK inhibitor SP600125 attenuated the IGF-1-induced stimulated phosphorylation of the Thr421/Ser424 sites on p70S6K1 but not that of the Thr389 site, and in combination with TORIN2 it blocked the effect of IGF1 on both sites. In contrast, inhibitors of the MAP kinase signaling pathway including UO126 and SB203580 had no effect on the IGF-1-induced stimulated phosphorylation of the Thr 389 and the Thr421/Ser424 sites whereas anisomycin, an activator of the JNK pathway specifically stimulated phosphorylation of the Thr421/Ser424 sites but not the Thr389 site. To assess a possible role for JNK in mediating phosphorylation of p70S6K1 on the Thr421/Ser424 sites in vivo, rats were treated with SP600125 6 h prior to tissue harvest following tenotomy. SP600125 attenuated the tenotomy-induced elevated phosphorylation of the Thr421/Ser424 sites on p70S6K1 but had no effect on that of Thr389. Phosphorylation of JNK was elevated following tenotomy and this was prevented by treatment with SP600125, providing additional evidence of a role for the JNK signaling pathway in mediating regulation of p70S6K1 in this experimental model of hypertrophic growth. Taken together, the results from these two experimental model systems demonstrate that both the mTORC1 and JNK signaling pathways contribute to the stimulation of cell growth by mediating site-specific phosphorylation of p70S6K1.

Subjects/Keywords: MAPK signaling; muscle hypertrophy; tenotomy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martin, T. D. (2014). An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading. (Masters Thesis). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/20079

Chicago Manual of Style (16^th Edition):

Martin, Tony Dewayne. “An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading.” 2014. Masters Thesis, Penn State University. Accessed November 20, 2019. https://etda.libraries.psu.edu/catalog/20079.

MLA Handbook (7^th Edition):

Martin, Tony Dewayne. “An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading.” 2014. Web. 20 Nov 2019.

Vancouver:

Martin TD. An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading. [Internet] [Masters thesis]. Penn State University; 2014. [cited 2019 Nov 20]. Available from: https://etda.libraries.psu.edu/catalog/20079.

Council of Science Editors:

Martin TD. An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading. [Masters Thesis]. Penn State University; 2014. Available from: https://etda.libraries.psu.edu/catalog/20079

University College Cork

6. O'Callaghan, Carol. Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma.

Degree: 2015, University College Cork

URL: http://hdl.handle.net/10468/2082

► Oesophageal cancer is an aggressive malignancy which is resistant to conventional therapy and has a poor prognosis. A greater understanding of the underlying molecular biology… (more)

▼ Oesophageal cancer is an aggressive malignancy which is resistant to conventional therapy and has a poor prognosis. A greater understanding of the underlying molecular biology of oesophageal cancer and the identification of novel targets is necessary for the future treatment of this disease. This thesis focuses specifically on the ill-defined and understudied p38δ mitogen-activated protein kinase (MAPK) and its function(s) in oesophageal squamous cell carcinoma (OESCC). In contrast to the three other p38 isoforms (p38α, -β and –γ which have to-date been relatively well-studied), p38δ MAPK signalling is poorly understood. Thus, this research elucidates some of the role(s) played by p38δ MAPK in cancer progression. This work outlines how loss of p38δ MAPK expression confers greater tumourigenicity in oesophageal cancer. Restoration of p38δ MAPK expression, however, has anti-proliferative and anti-migratory effects and decreases OESCC capacity for anchorageindependent growth. Using a novel application of an enzyme-substrate fusion approach, the effect of phosphorylated p38δ (p-p38δ) MAPK expression is also considered. The work goes onto describe the effect(s) of p38δ MAPK status on the chemosensitivity of OESCC to conventional cisplatin and 5-fluorouracil (CF) versus the effectiveness of doxorubicin, cisplatin and 5-fluorouracil (ACF). ACF treatment of p38δ MAPK-negative OESCC results in decreased proliferation, migration and recovery, and increased apoptosis when compared with CF treatment. This thesis examines the potential mechanisms by which p38δ MAPK expression is lost in OESCC and identifies epigenetic regulation as the probable cause of differential p38δ MAPK expression. Also analysed is the role p38δ MAPK and p-p38δ MAPK play in the cell cycle. In summary, this research identifies p38δ MAPK as a possible molecular target and a potential predictor of response to chemotherapy in OESCC patients. Advisors/Committee Members: Barry, Orla P., Fanning, Liam J., HRB.

Subjects/Keywords: Cancer; Oesophageal; p38; MAPK

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APA (6^th Edition):

O'Callaghan, C. (2015). Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma. (Thesis). University College Cork. Retrieved from http://hdl.handle.net/10468/2082

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

O'Callaghan, Carol. “Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma.” 2015. Thesis, University College Cork. Accessed November 20, 2019. http://hdl.handle.net/10468/2082.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

O'Callaghan, Carol. “Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma.” 2015. Web. 20 Nov 2019.

Vancouver:

O'Callaghan C. Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma. [Internet] [Thesis]. University College Cork; 2015. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/10468/2082.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

O'Callaghan C. Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma. [Thesis]. University College Cork; 2015. Available from: http://hdl.handle.net/10468/2082

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Notre Dame

7. Morgan Haugen. Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>.

Degree: MS, Biological Sciences, 2009, University of Notre Dame

URL: https://curate.nd.edu/show/8336h130n2q

► Prior to follicle selection, granulosa cells are actively maintained in an undifferentiated state by epidermal growth factor ligands (EGFL) that signal via the mitogen… (more)

Subjects/Keywords: MAPK signaling; Noggin; Id proteins

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APA (6^th Edition):

Haugen, M. (2009). Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>. (Masters Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/8336h130n2q

Chicago Manual of Style (16^th Edition):

Haugen, Morgan. “Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>.” 2009. Masters Thesis, University of Notre Dame. Accessed November 20, 2019. https://curate.nd.edu/show/8336h130n2q.

MLA Handbook (7^th Edition):

Haugen, Morgan. “Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>.” 2009. Web. 20 Nov 2019.

Vancouver:

Haugen M. Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>. [Internet] [Masters thesis]. University of Notre Dame; 2009. [cited 2019 Nov 20]. Available from: https://curate.nd.edu/show/8336h130n2q.

Council of Science Editors:

Haugen M. Inhibitory effects of bone morphogenetic proteins (BMPs) on hen granulosa cell differentiation</h1>. [Masters Thesis]. University of Notre Dame; 2009. Available from: https://curate.nd.edu/show/8336h130n2q

8. Gkouveris, Ioannis. Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος.

Degree: 2015, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/35601

► The oncogenetic role of STAT3 signaling molecule in oral squamous cell carcinoma.Gkouveris IoannisOral cancer is the sixth most common cancer worldwide and the incidence of… (more)

▼ The oncogenetic role of STAT3 signaling molecule in oral squamous cell carcinoma.Gkouveris IoannisOral cancer is the sixth most common cancer worldwide and the incidence of new cases indicates a continuing rise in developing countries. Several genetic and epigenetic alterations underlie the progressive acquisition of a malignant phenotypein head and neck squamous cell carcinoma (HNSCC). The molecular dissection of aberrant signaling networks, including EGFR, Ras, NF-κB, Wnt/β-catenin, TGF-β, and PI3K-AKT-mTOR signaling pathways, has increased our understanding on the basic mechanisms controlling HNSCC progression.Signal transducer and activator of transcription (STAT) proteins constitute a family of transcription factors, which exist in the cell as latent cytoplasmic transcription factors and become activated in response to stimulation by cytokines and growth factors, translocate to the nucleus, where they interact with the promoters of target genes. Phosphorylation of STAT molecules on a tyrosine residue is the first critical event for their activation and has been convincingly shown to correlate with STAT DNA binding and transcriptional activity. In contrast, STAT serine phosphorylation, which may also occur in response to growth factor and cytokine stimulation, has been associated mainly with negative regulation of STAT activity. STAT signaling has been found to be involved in oncogenesis There is compelling evidence that STAT3 constitutive activation, mainly associated with aberrant TGF-α/EGFR signaling, is linked to HNSCC development and growth.Mitogen-activated protein kinase (MAPK) pathways are evolutionarily conserved kinase modules that link extracellular signals to the machinery that controls fundamental cellular processes such as growth, proliferation, differentiation, migration and apoptosis. MAPKs phosphorylate serine and threonine residues of specific target proteins. They are classified into three major subfamilies, including extracellular signal-regulated kinases (ERKs), p38 MAPKs, and c-Jun NH2-terminal kinases (JNKs) Previous studies supported an association between activation of specific members of the MAPK family and negative regulation of STAT3, manifested by downregulation of STAT3 tyrosine phosphorylation and induction of STAT3 serine phosphorylation, in various cell types including cancer cells. PURPOSEThe aim of the present investigation was to evaluate whether oncogenic constitutive STAT3 signaling in oral squamous cell carcinoma (OSCC) cells can be modulated by regulation of specific MAPKs. The expression and activation status of STAT3 and MAPKs in HNSCC cell lines were recorded and the effects of selective MAPKs inhibition or activation on STAT3 signaling and cellular proliferation were monitored, in an attempt to elucidate important molecular aspects of oral cancer with potential therapeutic implications.MATERIAL AND METHODS Cell lines and cell culture. Experiments were performed using established cell lines…

Subjects/Keywords: Μεταγραφικοί παράγοντες STAT3; Σηματοδότηση; MAPK μονοπάτι μεταγωγής σήματος; Stat3; Signaling; Mapk

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gkouveris, I. (2015). Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/35601

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gkouveris, Ioannis. “Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος.” 2015. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed November 20, 2019. http://hdl.handle.net/10442/hedi/35601.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gkouveris, Ioannis. “Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος.” 2015. Web. 20 Nov 2019.

Vancouver:

Gkouveris I. Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2015. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/10442/hedi/35601.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gkouveris I. Ο ογκογενετικός ρόλος του σηματοδοτικού μορίου STAT3 στο ακανθοκυτταρικό καρκίνωμα του στόματος. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2015. Available from: http://hdl.handle.net/10442/hedi/35601

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. Haupaix, Nicolas. Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2014, Nice

URL: http://www.theses.fr/2014NICE4003

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Durant ma thèse, j’ai participé à une étude fonctionnelle qui a démontré que p120-RasGAP, une protéine appartenant à la famille GAP (GTPase-activating protein), est le… (more)

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Durant ma thèse, j’ai participé à une étude fonctionnelle qui a démontré que p120-RasGAP, une protéine appartenant à la famille GAP (GTPase-activating protein), est le médiateur cytoplasmique de l’éphrine lors de l’atténuation d’ERK1/2. Pour confirmer cela, j’ai réalisé une expérience de co-immunoprécipitation et j’ai démontré que p120-RasGAP s’associe au récepteur de l’éphrine, Eph3, quand celui-ci est activé par un ligand éphrine. Ce résultat indique fortement que les signaux FGF et éphrine convergent au niveau de Ras et qu’ils contrôlent de manière antagoniste son activité. Dès lors, j’ai analysé les autres événements de spécification cellulaire impliquant l’antagonisme FGF/éphrine. Chez l’embryon d’ascidie, le signal FGF est décrit comme inducteur du destin neural dans les cellules ectodermiques qui, en absence du signal FGF, adoptent le destin épidermique. L’induction neurale des ascidies a lieu au stade 32 cellules et se traduit par la spécification de quatre précurseurs neuraux (ERK+) parmi les 16 cellules ectodermiques. J’ai démontré que le signal éphrine/Eph/RasGAP antagonise le signal FGF pour générer une activation d’ERK1/2 de type tout ou rien parmi les cellules ectodermiques. Enfin, en collaboration avec Philip Abitua, doctorant dans le laboratoire du Dr. Mike Levine (UC Berkeley), nous démontrons que l’antagonisme entre les signaux éphrine et FGF est impliqué dans la régionalisation antéro-postérieure de la plaque neurale

During my thesis study, I was involved in functional studies to demonstrate that p120-RasGAP, a GTPase-activating-protein (GAP), is a cytoplasmic mediator of the ephrin-mediated ERK attenuation. To confirm this notion, I conducted a co-immunoprecipitation experiment and demonstrated that p120-RasGAP associates with an ephrin receptor, Eph3, when the latter is activated by an ephrin ligand in ascidian embryos. These results strongly indicate that FGF and ephrin signals converge at the level of Ras and control its activity antagonistically. Following this finding, I looked for other cell fate specification events controlled by the antagonism between ephrin and FGF signals. In ascidian embryos, FGF signals are known to induce neural fates in ectodermal cells which otherwise adopt epidermal fates. Ascidian neural induction takes place at the 32-cell stage, resulting in specification of specific four cells as ERK1/2-active neural precursors among 16 ectodermal cells. I was able to demonstrate that ephrin/Eph/RasGAP signals counterbalance FGF neural inducing signals to generate the ON-OFF response of ERK activation among the ectodermal cells. Finally, in collaboration with a PhD student in Dr. Mike Levine’s lab (UC Berkeley), the antagonism between ephrin and FGF signals plays a role in regionalisation of the neural plate along the anterior-posterior axis.

Advisors/Committee Members: Yasuo, Hitoyoshi (thesis director).

Subjects/Keywords: Ascidie; Spécification; MAPK; FGF; Éphrine; Ascidian; Specification; MAPK; FGF; Ephrin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Haupaix, N. (2014). Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis. (Doctoral Dissertation). Nice. Retrieved from http://www.theses.fr/2014NICE4003

Chicago Manual of Style (16^th Edition):

Haupaix, Nicolas. “Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis.” 2014. Doctoral Dissertation, Nice. Accessed November 20, 2019. http://www.theses.fr/2014NICE4003.

MLA Handbook (7^th Edition):

Haupaix, Nicolas. “Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis.” 2014. Web. 20 Nov 2019.

Vancouver:

Haupaix N. Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis. [Internet] [Doctoral dissertation]. Nice; 2014. [cited 2019 Nov 20]. Available from: http://www.theses.fr/2014NICE4003.

Council of Science Editors:

Haupaix N. Régulation de la voie MEK/ERK par la signalisation éphrine lors du développement neural chez l'ascidie Ciona intestinalis : MEK/ERK regulation by the ephrin pathway during neural development in ascidian Ciona intestinalis. [Doctoral Dissertation]. Nice; 2014. Available from: http://www.theses.fr/2014NICE4003

10. Renaud, Emilie. Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments.

Degree: Docteur es, Biologie Santé, 2018, Montpellier

URL: http://www.theses.fr/2018MONTT088

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La MAPK p38α est une protéine clé de l’inflammation, également impliquée dans de nombreux processus liés au cancer. Les petites molécules chimiques inhibitrices de p38α… (more)

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La MAPK p38α est une protéine clé de l’inflammation, également impliquée dans de nombreux processus liés au cancer. Les petites molécules chimiques inhibitrices de p38α bloquent son activité kinase par un mécanisme de compétition à l’ATP. En raison de la grande conservation du domaine kinase, la spécificité de la majorité de ces inhibiteurs n’est pas restreinte à la p38α et des effets « off-targets » ont été rapportés. Dans ce contexte, le projet de ma thèse a porté sur l’utilisation de fragments d’anticorps au format scFv comme nouvel outil de ciblage pharmacologique afin de définir une/des voie(s) alternative(s) d’inhibition de la p38α. Les fragments d’anticorps lient un motif antigénique avec une affinité et une spécificité élevées, tout comme les immunoglobulines classiques. Leur expression intracellulaire permet également le ciblage de protéines cytoplasmiques et l’étude de leurs fonctions dans des processus physiologiques et pathologiques. Nous avons sélectionné par phage display, à partir d’une banque de fragments d’anticorps, 5 scFv spécifiques de la MAPK p38α. Alors que tous ces scFv empêchent l’activation par phosphorylation de la p38α par MKK6, l’un d’entre eux agit directement sur l’enzyme pour inhiber totalement son activité kinase in vitro. Ce scFv possède un site de liaison et un mécanisme d’inhibition distincts des inhibiteurs pharmacologiques déjà décrits : bien qu’il ne cible pas le domaine kinase et n’empêche pas la fixation de l’ATP, le scFv se comporte comme un inhibiteur compétitif de l’hydrolyse de l’ATP. Ces résultats suggèrent un effet allostérique du scFv sur l’activité de la p38α et permettent de le caractériser comme un inhibiteur compétitif non conventionnel. La détermination de son épitope d‘interaction ainsi que la confirmation de sa fonctionnalité une fois exprimé dans le cytosol des cellules nous permettra de définir une voie alternative d'inhibition de la p38α et de valider notre approche de ciblage par l’utilisation de fragments d’anticorps.Ces données ouvrent de nouvelles perspectives de design d’inhibiteurs chimiques de la p38α de meilleure spécificité que ceux actuellement disponibles.

MAPK p38α is a key protein in inflammation, but is also involved in many cancer-related processes. All the currently described chemical inhibitors of p38α inhibit its kinase activity by an ATP-competitive mechanism. Because of the high conservation of the ATP-binding pocket, the majority of these inhibitors are not specific to p38α and off-target effects have been reported. To identify alternative approaches to inhibit p38α MAPK, my thesis project focused on the use of scFv antibody fragments as a new highly specific pharmacological tool.Antibody fragments bind to an antigen with high affinity and specificity like conventional immunoglobulins. Their intracellular expression also allows to target cytoplasmic proteins and study the target functions in physiological and pathological processes. Using a naïve library of antibody fragments, we have selected by phage display five scFv specific of MAPK…

Advisors/Committee Members: Guglielmi, Laurence (thesis director).

Subjects/Keywords: MAPK p38α; ScFv; Inhibiteur allostérique; MAPK p38α; ScFv; Allosteric inhibitor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Renaud, E. (2018). Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2018MONTT088

Chicago Manual of Style (16^th Edition):

Renaud, Emilie. “Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments.” 2018. Doctoral Dissertation, Montpellier. Accessed November 20, 2019. http://www.theses.fr/2018MONTT088.

MLA Handbook (7^th Edition):

Renaud, Emilie. “Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments.” 2018. Web. 20 Nov 2019.

Vancouver:

Renaud E. Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments. [Internet] [Doctoral dissertation]. Montpellier; 2018. [cited 2019 Nov 20]. Available from: http://www.theses.fr/2018MONTT088.

Council of Science Editors:

Renaud E. Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps : Isoform-specific inhibition of MAPK p38α functions by antibody fragments. [Doctoral Dissertation]. Montpellier; 2018. Available from: http://www.theses.fr/2018MONTT088

11. Schick, Ulrike. Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma.

Degree: Docteur es, Biologie moléculaire et cellulaire, 2015, Paris Saclay

URL: http://www.theses.fr/2015SACLS151

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Il est fréquent d’avoir recours à la radiothérapie dans le traitement des mélanomes, en adjuvant ou en métastatique, mais les résultats cliniques sont suboptimaux, car… (more)

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Il est fréquent d’avoir recours à la radiothérapie dans le traitement des mélanomes, en adjuvant ou en métastatique, mais les résultats cliniques sont suboptimaux, car ces tumeurs présentent souvent des mutations de RAF/RAS, activant alors la voie MAPK de façon constitutive. Nous avons donc étudier si le Trametinib, un inhibiteur allostérique puissant et sélectif de MEK1/2, est en mesure d’augmenter l’efficacité de la radiothérapie. Des tests clonogéniques ont été effectués sur des lignées de mélanomes humaines mutées pour BRAF (A375), NRAS (D04,WM1631), KRAS (WM1791c) ainsi que sur une lignée sauvage (PMWK). Les effets du Tramétinib avec ou sans irradiation (IR) sur les protéines effectrices de MEK ont été quantifiés par western-blot. Les effets de l’addition du Trametinib sur le cycle cellulaire, la réparation de l’ADN, la catastrophe mitotique et la senescence ont respectivement été analysés par cytométrie de flux, étude des foyers γH2Ax, et marquage de l’activité de la β-galactosidase. Enfin, des souris immunodéficientes xenogreffées avec des cellules D04 ont été traitées par IR fractionnée après gavage de Trametinib, et la croissance tumorale a été monitorée.Une augmentation de la cytocoxité en présence de l’ajout de Trametinib à l’ IR a été observée pour toutes les lignées, exceptée PMWK. Le taux de radiosensibilisation des cellules étaient respectivement de 1.70, 1.32, 1.22, et 1.70 pour A375, D04, WM1361 et WM1791c. Le Trametinib bloquait de façon efficace la phosphrylation de ERK à des doses de l’ordre du nanomolaire. Ceci corrélait avec un arrêt prolongé des cellules en phase G1, et une réduction de la phase S, connue pour être radiosésistante, ceci jusqu’à 48 heures après IR. Dans les groupes cellulaires prétraités par Trametinib, une population plus importante de cellules étaient positives pour la β-galactosidase, et deux médiateurs majeurs de la sénescence, p53 et pRb se trouvaient être activés. Les souris recevant le traitement combiné (Trametinib 1mg/kg et IR sur 3 jours) avaient un volume tumoral réduit en comparaison du groupe recevant du Trametinib seul (p=0.016), ou une IR seule (p=0.047). Il n’y avait pas de toxicité notable dans le groupe recevant le traitement combiné.Le Trametinib radiosensibilise les lignées cellulaires de mélanomes mutées pour RAF/RAS en induisant un arrêt prolongé en phase G1 du cycle cellulaire, provoquant ainsi une sénescence prématurée. Associer Trametinib et IR semble être parfaitement toléré, mais ne ralentit la croissance tumorale que modestement in vivo.

Radiotherapy is used frequently in patients with melanoma, but results are suboptimal as these tumours frequently exhibit constitutive activation of the MAPK pathway through mutations involving RAS/RAF. Thus, we studied whether Trametinib, a potent and selective allosteric inhibitor of the MEK1/2 enzymes could improve efficacy of radiotherapy.Clonogenic survival assays were carried out in human BRAF (A375), NRAS (D04,WM1631), KRAS (WM1791c) mutant and wild type (PMWK) melanoma. The effects of Trametinib with and…

Advisors/Committee Members: Deutsch, Eric (thesis director), Harrington, Kevin J. (thesis director).

Subjects/Keywords: Voie MAPK; Radiosensibilisation; Mélanomes; Trametinib; MAPK pathway; Radiosensitisation; Melanoma; Trametinib

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schick, U. (2015). Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma. (Doctoral Dissertation). Paris Saclay. Retrieved from http://www.theses.fr/2015SACLS151

Chicago Manual of Style (16^th Edition):

Schick, Ulrike. “Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma.” 2015. Doctoral Dissertation, Paris Saclay. Accessed November 20, 2019. http://www.theses.fr/2015SACLS151.

MLA Handbook (7^th Edition):

Schick, Ulrike. “Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma.” 2015. Web. 20 Nov 2019.

Vancouver:

Schick U. Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma. [Internet] [Doctoral dissertation]. Paris Saclay; 2015. [cited 2019 Nov 20]. Available from: http://www.theses.fr/2015SACLS151.

Council of Science Editors:

Schick U. Modulation pharmacologique de la radiosensibilité tumorale des mélanomes par inhibition de MEK : Investigating the in vitro and in vivo radiosensitizing effect of MEK inhibition in melanoma. [Doctoral Dissertation]. Paris Saclay; 2015. Available from: http://www.theses.fr/2015SACLS151

University of Toledo

12. Zhan, Yu. Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2.

Degree: PhD, Biology (Cell-Molecular Biology), 2011, University of Toledo

URL: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310127039

► Mixed lineage kinase 3 (MLK3), a 97 kDa Ser/Thr protein kinase, is a MAP kinase kinase kinase (MAP3K) that phosphorylates and activates MAP kinase kinases… (more)

▼ Mixed lineage kinase 3 (MLK3), a 97 kDa Ser/Thr protein kinase, is a MAP kinase kinase kinase (MAP3K) that phosphorylates and activates MAP kinase kinases (MAP2Ks), resulting in the activation of JNK, p38 and ERK MAPK pathways. The Rho GTPases Rac and Cdc42, activate MLK3 via binding to the CRIB domain of MLK3, relieving the SH3 mediated auto-inhibition, and promoting MLK3 auto-phosphorylation and activation. Though the role of MLK3 in tumorigenesis is still under investigation, previous studies have indicated that MLK3 can transform NIH3T3 cells in a MEK dependent manner, and recently, MLK3 expression was found to induce invasion in mammary epithelial cells. In addition, our results indicate higher MLK3 expression and kinase activity in SKOV3, HEY and HEY1B ovarian tumor cells in comparison to immortalized ovarian epithelial T29 and T80 cells. Thus, we hypothesized that MLK3 could promote aberrant MAPK activity and cell invasion in ovarian cancer cells. In our study, we found that silencing mlk3 substantially reduced ERK and JNK signaling, cell invasion, and matrix metalloproteinases (MMP)-1, -2, -9 and -12 expression in SKOV3 cells. Thus we propose that MLK3 may promote invasion by up-regulating specific MMP expression in ovarian cancer cells.The Neurofibromatosis Type 2 (NF2) gene encodes a 595 amino acid tumor suppressor protein, merlin, which has homology to the Ezrin, Radixin and Moesin (ERM) group of cellular proteins that link integral membrane proteins to the actin cytoskeleton. Merlin undergoes intramolecular interactions between the N-terminus and C-terminus, and phosphorylation on Ser518 inhibits this interaction and inactivates merlin. Activated merlin inhibits cell proliferation, cell cycle progression and motility, however, a detailed biochemical mechanism for the growth suppressive function of merlin remains elusive. We previously found that merlin is a MLK3 inhibitor, and we wished to investigate if MLK3 is required for merlin-mediated suppression of cell growth, invasion and MAPK signaling in ovarian and NF2 tumor cells. Comparison of different human cell lines revealed high basal MLK3 activity in HEI193, SKOV3 and NCIH460 cell lines. Interestingly, there was a correlation between high MLK3 activity and reduced merlin expression in the tumor cell lines. The carboxyl-terminus of merlin (340-590) is required for merlin-MLK3 interaction, and is sufficient to inhibit MLK3 kinase acitivity. Induction of merlin protein expression in RT4-NF2.17 cells (rat schwannoma cells with Tet-inducible merlin) inhibited MLK3, B-Raf, ERK and JNK activities. In contrast, depletion of merlin elevated MLK3, B-Raf, ERK and JNK activities. Merlin expression blocked the interaction between MLK3 and the upstream activator, Rho GTPase, Cdc42. In addition, MLK3 was required for proliferation and invasion of cells that lacked functional merlin.Our data suggests that merlin inhibits MLK3 by blocking the cdc42-MLK3 interaction, and that elevated basal MLK3 activity in NF2, ovarian and other tumor cells may be due to the loss of… Advisors/Committee Members: Chadee, Deborah (Advisor).

Subjects/Keywords: Biology; MLK3; merlin; NF2; Ovarian cancer; MAPK

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhan, Y. (2011). Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2. (Doctoral Dissertation). University of Toledo. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310127039

Chicago Manual of Style (16^th Edition):

Zhan, Yu. “Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2.” 2011. Doctoral Dissertation, University of Toledo. Accessed November 20, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310127039.

MLA Handbook (7^th Edition):

Zhan, Yu. “Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2.” 2011. Web. 20 Nov 2019.

Vancouver:

Zhan Y. Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2. [Internet] [Doctoral dissertation]. University of Toledo; 2011. [cited 2019 Nov 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310127039.

Council of Science Editors:

Zhan Y. Mixed Lineage Kinase 3 Signaling in Ovarian Cancer and Neurofibromatosis-2. [Doctoral Dissertation]. University of Toledo; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310127039

NSYSU

13. Hsu, Cheng-yuan. The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells.

Degree: Master, Biological Sciences, 2004, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456

► Nasopharyngeal carcinoma (NPC) occurs occasionally in the west but is popular in south-eastern China and Hong Kong where it is the third most common form… (more)

▼ Nasopharyngeal carcinoma (NPC) occurs occasionally in the west but is popular in south-eastern China and Hong Kong where it is the third most common form of malignancy among ethnic Chinese people. The possibly relevant factors associated with NPC have been found, for example, environment, genetics and EB virus, etc. Recently, as a result of improved environment of living and therapies, the death rate of NPC is decreasing year by year. However, the molecules mechanism underlying its tumorigenicity is still unclear. The p57 protein is a maternally expressed, paternally imprinted cyclin-dependent kinases inhibitor (CDI). p57 mutations are rare in the human cancers, suggesting that other mechanisms of transcriptional or post translational silencing are involved in the loss of p57 function. Decreased expression of p57 has been found in Beckwith-Wiedemann syndrome (BWS), gastric cancer and bladder carcinoma. So far, many studies in signal transduction have been focused on p21 or p27. The relationship between p57 expression and signal transduction and cell proliferation under physiological circumstances requires further exploration. Studies of the relationship between hormones and cancers have been proceeded for years, nevertheless, there is few about NPC. We examined several hormonesâ effect on the NPC cell lines. We found that in response to progesterone treatment were the marked inhibition of pMAPK and up-regulation of p57, just like the influence of MEK inhibitor, U0126. Progesterone also induced growth inhibition and a slight accumulation of cells in the G1 phase of the cell cycle. On the other hand, the effects of progesterone were diminished in the presence of its antagonist mifepristone (RU-486). Taken together, these results suggest that progesterone treatment may induce the expression of the p57 on the mRNA and protein level by the progesterone receptor and that the MAPK signaling pathway may be involved in the progesterone-induced antiproliferative effect. Advisors/Committee Members: Pei-jung Lu (chair), Hung-sheng Hsiao (chair), Chung-lung Cho (committee member), Hong-yu Kang (chair).

Subjects/Keywords: p57KIP2; MAPK; progesterone

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hsu, C. (2004). The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hsu, Cheng-yuan. “The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells.” 2004. Thesis, NSYSU. Accessed November 20, 2019. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hsu, Cheng-yuan. “The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells.” 2004. Web. 20 Nov 2019.

Vancouver:

Hsu C. The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells. [Internet] [Thesis]. NSYSU; 2004. [cited 2019 Nov 20]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hsu C. The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells. [Thesis]. NSYSU; 2004. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0914104-101456

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Western Australia

14. Azzam, Diana Galil. Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells.

Degree: PhD, 2008, University of Western Australia

URL: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=5804&local_base=GEN01-INS01

► [Truncated abstract] Androgens inhibit the growth of human breast tumours and have been successfully used to treat breast cancer in women. Expression of the androgen… (more)

▼ [Truncated abstract] Androgens inhibit the growth of human breast tumours and have been successfully used to treat breast cancer in women. Expression of the androgen receptor (AR), which mediates androgen action, is upregulated in breast cancer cells and the AR is the most frequently expressed steroid hormone receptor in breast tumours. AR levels and activity are modulated by the activity of other signalling pathways, however interactions between the AR and signalling pathways and the consequent alterations to the androgen responsiveness of breast cancer cells are largely uncharacterised. The extracellular signal regulated kinase (ERK1/2) pathway is hyperactivated in ~30% of breast tumours and these tumours are often associated with low oestrogen receptor-α (ERα) levels, reduced responsiveness to antioestrogen therapies and an overall poorer prognosis. In this thesis, the MCF-7 human breast cancer cell line which expresses ERα, progesterone receptor (PR) and the AR, was used to investigate ERK1/2-mediated regulation of the AR and the androgen responsiveness of cells. Inhibition of ERK1/2 signalling was achieved by treatment of cells with U0126, an inhibitor of MEK1/2, the upstream activator of ERK1/2. Hyperactivation of ERK1/2 signalling was achieved by stably transfecting cells with a plasmid encoding a constitutively active form of the MEK1 protein (ΔMEK1), resulting in the isolation of two clonal cell populations stably expressing ΔMEK1, ΔC3 and Δ6B, and a monoclonal cell line stably expressing the empty vector, MT3-1. Steady state AR mRNA levels, quantitated using real-time RT-PCR, were increased following U0126 treatment of MCF-7, MT3-1 and Δ6B cells. Conversely, treatment of cells with 10-8M 5α-dihydrotestosterone (DHT) for up to 72 hours decreased AR mRNA levels, indicating that ERK1/2 hyperactivation did not alter the androgenresponsiveness of AR mRNA. '...' Overall levels of AR phosphorylation were enhanced in Δ6B cells in the absence and presence of ligand, indicating that ERK1/2 hyperactivation either directly or indirectly induced receptor phosphorylation. The AR is localised in the cytoplasm in the absence of ligand and was more rapidly translocated to the nucleus in the presence of DHT in ΔC3 cells, an effect that was abrogated in the presence of U0126, thereby indicating an ERK1/2-specific mechanism. AR transcriptional activity, measured using androgen responsive reporter plasmids was not significantly altered in Δ6B cells in either the absence or presence of DHT, although the trend towards enhanced AR activity may be confirmed in future studies using optimised reporter assays. Consistent with the cell cycle regulatory functions of ERK1/2 signalling, proliferation of ΔC3 cells and Δ6B cells was increased in comparison to that of MT3-1 and MCF-7 cells. Treatment of ΔC3 cells and MCF-7 cells with 10-10 – 10-8M DHT produced similar inhibition of proliferation (~40%) during 8 days of culture, with no evidence of cytotoxicity. The results obtained in this thesis demonstrate that while ERK1/2 signalling…

Subjects/Keywords: Breast; Androgens; Protein kinases; MAPK signalling

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APA (6^th Edition):

Azzam, D. G. (2008). Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells. (Doctoral Dissertation). University of Western Australia. Retrieved from http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=5804&local_base=GEN01-INS01

Chicago Manual of Style (16^th Edition):

Azzam, Diana Galil. “Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells.” 2008. Doctoral Dissertation, University of Western Australia. Accessed November 20, 2019. http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=5804&local_base=GEN01-INS01.

MLA Handbook (7^th Edition):

Azzam, Diana Galil. “Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells.” 2008. Web. 20 Nov 2019.

Vancouver:

Azzam DG. Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells. [Internet] [Doctoral dissertation]. University of Western Australia; 2008. [cited 2019 Nov 20]. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=5804&local_base=GEN01-INS01.

Council of Science Editors:

Azzam DG. Extracellular signal regulated kinase/mitogen activated protein kinase (ERK/MAPK) regulation of the androgen receptor in breast cancer cells. [Doctoral Dissertation]. University of Western Australia; 2008. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=5804&local_base=GEN01-INS01

University of Louisville

15. Aulakh, Kavita Burman. Specific b alleles matter in phytopathogenic Ustilago maydis.

Degree: MS, 2012, University of Louisville

URL: 10.18297/etd/57 ; https://ir.library.louisville.edu/etd/57

► The smut fungus, Usti/ago maydis is an obligate parasite on maize plants in order to complete its sexual life cycle. The haploid form is self-sterile… (more)

Subjects/Keywords: Phytopathogenic; PAK; Ustilago maydis; PKA; MAPK; Mating

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APA (6^th Edition):

Aulakh, K. B. (2012). Specific b alleles matter in phytopathogenic Ustilago maydis. (Masters Thesis). University of Louisville. Retrieved from 10.18297/etd/57 ; https://ir.library.louisville.edu/etd/57

Chicago Manual of Style (16^th Edition):

Aulakh, Kavita Burman. “Specific b alleles matter in phytopathogenic Ustilago maydis.” 2012. Masters Thesis, University of Louisville. Accessed November 20, 2019. 10.18297/etd/57 ; https://ir.library.louisville.edu/etd/57.

MLA Handbook (7^th Edition):

Aulakh, Kavita Burman. “Specific b alleles matter in phytopathogenic Ustilago maydis.” 2012. Web. 20 Nov 2019.

Vancouver:

Aulakh KB. Specific b alleles matter in phytopathogenic Ustilago maydis. [Internet] [Masters thesis]. University of Louisville; 2012. [cited 2019 Nov 20]. Available from: 10.18297/etd/57 ; https://ir.library.louisville.edu/etd/57.

Council of Science Editors:

Aulakh KB. Specific b alleles matter in phytopathogenic Ustilago maydis. [Masters Thesis]. University of Louisville; 2012. Available from: 10.18297/etd/57 ; https://ir.library.louisville.edu/etd/57

University of Manchester

16. Gaffey, Kate. Glucocorticoid resistance in COPD : the role of p38 MAPK.

Degree: PhD, 2013, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574385

► Chronic Obstructive Pulmonary Disease (COPD) is a chronic, inflammatory condition, characterised by airflow limitation. The use of glucocorticoids (GC) as an anti-inflammatory treatment in COPD… (more)

▼ Chronic Obstructive Pulmonary Disease (COPD) is a chronic, inflammatory condition, characterised by airflow limitation. The use of glucocorticoids (GC) as an anti-inflammatory treatment in COPD has limited clinical benefits, and as such, new treatments are needed. Identifying key pathways involved in the inflammatory response in COPD may enable the development of novel treatments. The aims of this thesis were to examine the steroid sensitivity of an in vitro mixed sputum culture cell model, comparing COPD cells to smoking and non-smoking controls, examine expression of the intracellular signalling molecule p38 Mitogen Activated Protein Kinase (MAPK) in COPD lungs compared with controls, examine the GC and p38 MAPK inhibitor and dual therapy sensitivity of a bronchial epithelial cell line and finally, to understand the mechanisms by which a p38 MAPK inhibitor in combination with a GC synergistically inhibit pro-inflammatory mediator production in a bronchial epithelial cell line. Dexamethasone inhibits mixed sputum cell pro-inflammatory mediator release, with no differences in sensitivity observed between COPD and control cells. Isolated sputum neutrophils demonstrate modest sensitivity to dexamethasone, which is in contrast to blood neutrophils. There are increased numbers of cells positive for activated p38 MAPK in COPD lungs compared with controls, specifically localised to follicular B and CD8+ T cells, bronchial epithelial cells and alveolar and sputum macrophages. Lung and sputum neutrophils are devoid of activated p38 MAPK, and a pharmacological p38 MAPK inhibitor has no effect on pro-inflammatory mediator production from these cells. This is in contrast to blood neutrophils, whereby p38 MAPK activation can be induced following LPS stimulation and in vitro cell culture, and pro-inflammatory mediator release is inhibited by a p38 MAPK inhibitor. Dexamethasone and birb 796 inhibit stimulated pro-inflammatory mediator release from a bronchial epithelial cell line in a dose-dependent manner. Sensitivity to either drug is dependent on stimuli and the pro-inflammatory mediator analysed. There is additive and synergistic inhibition of pro-inflammatory mediator production when combination therapy comprising dexamethasone and birb 796 is used compared with either drug alone. This may be due to Birb 796 enhancing dexamethasone-mediated nuclear translocation of the glucocorticoid receptor, which may enhance the GC-mediated anti-inflammatory effects. Combination therapy may therefore be a useful therapeutic in the treatment of COPD.

Subjects/Keywords: 616.24; COPD; inflammation; glucocorticoid resistance; p38 MAPK

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APA (6^th Edition):

Gaffey, K. (2013). Glucocorticoid resistance in COPD : the role of p38 MAPK. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574385

Chicago Manual of Style (16^th Edition):

Gaffey, Kate. “Glucocorticoid resistance in COPD : the role of p38 MAPK.” 2013. Doctoral Dissertation, University of Manchester. Accessed November 20, 2019. https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574385.

MLA Handbook (7^th Edition):

Gaffey, Kate. “Glucocorticoid resistance in COPD : the role of p38 MAPK.” 2013. Web. 20 Nov 2019.

Vancouver:

Gaffey K. Glucocorticoid resistance in COPD : the role of p38 MAPK. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2019 Nov 20]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574385.

Council of Science Editors:

Gaffey K. Glucocorticoid resistance in COPD : the role of p38 MAPK. [Doctoral Dissertation]. University of Manchester; 2013. Available from: https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574385

University of Manchester

17. Maddison, Louise Elizabeth. Experimental and Theoretical Modelling of the MAPK Pathway.

Degree: 2012, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:167012

►

The MAPK pathway plays a crucial role in regulating cellular response to external stimuli. Binding of growth factors and other mitogenic signals to cell surface… (more)

▼

The MAPK pathway plays a crucial role in regulating cellular response to external stimuli. Binding of growth factors and other mitogenic signals to cell surface receptors initiates a phosphorylation-dependent relay of protein activation, resulting in altered transcription, ultimately regulating cell proliferation and differentiation. Signalling through this pathway is regulated by the coordinated function of specific protein kinases and protein phosphatases. As perturbation of this signalling system is often associated with diseases such as cancer, modelling is a useful means to help understand the outcomes that may result following changes in component levels or activity. The determination of absolute quantification data, in copies per cell, for proteins of the MAPK pathway will allow the expansion of and improved accuracy within predictive models.The strategy used within this thesis is based on the established technique of stable isotope dilution, generating isotopically labelled peptides using the QconCAT methodology. Recombinant DNA techniques were used to generate artificial concatamers of large numbers of tryptic peptides as quantification standards. A QconCAT, LM1, of 49 KDa (29 tryptic peptides), corresponding to the scaffold proteins was designed and built to encode two peptides per protein. A second QconCAT, LM2, of 58 KDa (34 tryptic peptides), encoded peptides from the dual-specificity phosphatases (DUSPs) and substrates. Quantification was performed using ultra performance liquid chromatography coupled to mass spectrometry. A selected reaction monitoring (SRM) approach was employed where the most intense y-ions per peptide were selected either from experimental data or predictions in silico. Using the ratio of the signal for the light:heavy isotopologues, the amount of light isotopologue can be inferred, allowing copies per cell quantifications to be established. Native peptides were present below the lower limit of quantification, and therefore the upper bounds of copies per cell were obtained for the three cell lines; colon cancer cells HCT 116 (K-Ras mutant) and HT-29 (B-Raf mutant) and a control cell line of HEK-293. Finally, mathematical modelling was undertaken to explore the mass-action kinetics of a three component scaffold signalling molecule. It was found that the optimal scaffold concentration is between the lowest and second lowest concentration of signalling protein.

An emerging research field, known as Systems Biology, has the potential to provide a vital link to new drug discoveries to combat cancer. Systems Biology combines laboratory results and specialised software to simulate human cells in the computer. By working with these virtual cells, new insights into the disease can be revealed. Cells communicate to each other across a complex network of protein to protein interactions. When a small molecule known as a growth factor attaches to the outside of the cell, a relay of signals is stimulated. These signals travel through the cell to reach the nucleus. The nucleus holds the genetic…

Advisors/Committee Members: WESTERHOFF, HANS HV, Eyers, Claire, Westerhoff, Hans.

Subjects/Keywords: MAPK; Systems Biology; Mathematical Modelling; Mass Spectrometry

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APA (6^th Edition):

Maddison, L. E. (2012). Experimental and Theoretical Modelling of the MAPK Pathway. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:167012

Chicago Manual of Style (16^th Edition):

Maddison, Louise Elizabeth. “Experimental and Theoretical Modelling of the MAPK Pathway.” 2012. Doctoral Dissertation, University of Manchester. Accessed November 20, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:167012.

MLA Handbook (7^th Edition):

Maddison, Louise Elizabeth. “Experimental and Theoretical Modelling of the MAPK Pathway.” 2012. Web. 20 Nov 2019.

Vancouver:

Maddison LE. Experimental and Theoretical Modelling of the MAPK Pathway. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2019 Nov 20]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:167012.

Council of Science Editors:

Maddison LE. Experimental and Theoretical Modelling of the MAPK Pathway. [Doctoral Dissertation]. University of Manchester; 2012. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:167012

Université de Sherbrooke

18. Couture, Jean-Philippe. Rôle de la MAPKKK DLK dans l'adipogenèse .

Degree: 2011, Université de Sherbrooke

URL: http://savoirs.usherbrooke.ca/handle/11143/5160

► Depuis plusieurs années, le tissu adipeux est reconnu comme un organe complexe et extrêmement important au maintien de l'homéostasie chez les mammifères. En effet, une… (more)

▼ Depuis plusieurs années, le tissu adipeux est reconnu comme un organe complexe et extrêmement important au maintien de l'homéostasie chez les mammifères. En effet, une dérégulation de sa taille et/ou de ses fonctions endocrines peut mener à l'apparition de nombreuses pathologies potentiellement mortelles, telles que le diabète de type II, l'hypertension ou encore des troubles cardiovasculaires. Ainsi, il est d'une importance capitale de bien comprendre les phénomènes moléculaires qui entourent la différenciation des cellules graisseuses afin de mieux réagir en clinique lors de l'apparition de telles conditions. Dans cette thèse, j'ai étudié le rôle d'une protéine kinase appelée dual leucine zipper-bearing kinase (DLK) dans la formation du tissu graisseux en utilisant un modèle cellulaire murin à différenciation inductible, les 3T3-L1. À l'aide d'approches pharmacologiques et d'ARN interférence, j'ai pu démontrer que cette protéine est essentielle à l'adipogenèse. En effet, une diminution de l'expression de DLK dans les cellules 3T3-L1 bloque la différenciation à un stade précoce, i.e. entre la liaison du facteur de transcription C/EBP[béta] à l'ADN et l'expression de ses gènes cibles, tels que C/EBP[alpha] et PPAR[gamma]. L'étude plus poussée des voies de signalisation des MAPKs à l'aide d'inhibiteurs pharmacologiques dans des cellules où l'expression de DLK a été diminuée a révélé que l'action bénéfique de DLK lors de la différenciation se situe au niveau de la voie ERK. En effet, l'induction de DLK au cours de l'adipogenèse résulte en une diminution de l'association des protéines KSR-1, Mek et ERK, ce qui mène à une diminution temporaire de l'activité de ERK et de la phosphorylation inhibitrice sur la sérine 82 du régulateur central de la différenciation des adipocytes, PPAR[gamma]. Finalement, nous avons pu déterminer que l'induction de DLK au cours de la différenciation des cellules graisseuses est modulée par PPAR[gamma]. Advisors/Committee Members: Blouin, Richard (advisor).

Subjects/Keywords: MAPK; Signalisation cellulaire; Adipocytes; Adipogenèse; DLK

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APA (6^th Edition):

Couture, J. (2011). Rôle de la MAPKKK DLK dans l'adipogenèse . (Doctoral Dissertation). Université de Sherbrooke. Retrieved from http://savoirs.usherbrooke.ca/handle/11143/5160

Chicago Manual of Style (16^th Edition):

Couture, Jean-Philippe. “Rôle de la MAPKKK DLK dans l'adipogenèse .” 2011. Doctoral Dissertation, Université de Sherbrooke. Accessed November 20, 2019. http://savoirs.usherbrooke.ca/handle/11143/5160.

MLA Handbook (7^th Edition):

Couture, Jean-Philippe. “Rôle de la MAPKKK DLK dans l'adipogenèse .” 2011. Web. 20 Nov 2019.

Vancouver:

Couture J. Rôle de la MAPKKK DLK dans l'adipogenèse . [Internet] [Doctoral dissertation]. Université de Sherbrooke; 2011. [cited 2019 Nov 20]. Available from: http://savoirs.usherbrooke.ca/handle/11143/5160.

Council of Science Editors:

Couture J. Rôle de la MAPKKK DLK dans l'adipogenèse . [Doctoral Dissertation]. Université de Sherbrooke; 2011. Available from: http://savoirs.usherbrooke.ca/handle/11143/5160

Wright State University

19. Vallabhaneni, Sreeram. Investigating the Function of ERK3 In Lung Tumor Progression.

Degree: MS, Biochemistry and Molecular Biology, 2018, Wright State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1526077960269769

► Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) involved in cell growth and differentiation. Recent studies have revealed important roles for… (more)

▼ Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) involved in cell growth and differentiation. Recent studies have revealed important roles for ERK3 in promoting cancer cell migration and invasion. In addition, ERK3 was shown to be highly upregulated in human lung cancers and to be associated with tumor metastasis. Altogether, these findings suggest an important role for ERK3 in lung tumor formation and progression. However, no in vivo study of ERK3 in lung tumorigenesis has been reported. For this purpose, a transgenic mouse model conditionally overexpressing ERK3 in lung bronchial epithelial cells was generated. First, a transgenic mouse line harboring ERK3 transgene under the control of a ubiquitous promoter and a STOP sequence flanked by two Lox P sites (LSL-ERK3) was generated. The obtained LSL-ERK3 mice were then crossed with a mouse line harboring the Cre recombinase transgene driven by a Clara cell secretory protein gene promoter (CCSP-Cre), resulting in CCSP-Cre/LSL-ERK3 transgenic mice that show ERK3 overexpression in Clara cells, the non-ciliated epithelial cells lining the bronchioles of lung. No clear phenotype, however, was observed in CCSP-Cre/LSL-ERK3 transgenic mice. As lung tumorigenesis usually requires multiple genetic alterations, the CCSP-Cre/LSL-ERK3 transgenic mice were then crossed with a PTENFlox/Flox mouse line in which the exon 5 of the tumor suppressor gene PTEN (Phosphatase and Tensin homolog) is flanked by two Lox P sites. These crossings led to the generation of CCSP-Cre/LSL-ERK3/PTENFlox/Flox mice which display PTEN deletion and ERK3 overexpression in the Clara cells of lung. Thus, four transgenic mouse groups were included in the study and monitored on daily basis: 1) LSL-ERK3; 2) CCSP-Cre/LSL-ERK3; 3) CCSP-Cre/PTENFlox/Flox; 4) CCSP-Cre/LSL-ERK3/PTENFlox/Flox. Tumor growth or other abnormalities in the lungs were analyzed by examining the whole lungs for surface tumors and by histological examination of lung tissue sections. As reported in previous studies, PTEN deletion alone resulted in lung hyperplasia. Interestingly, while ERK3 overexpression alone didn’t cause clear phenotype, a combination of ERK3 overexpression with PTEN deletion in CCSP-Cre/LSL-ERK3/ PTENFlox/Flox mice induced lung tumorigenesis as demonstrated by the formation of surface tumors in lungs. Tumor formation in these CCSP-Cre/LSL-ERK3/PTENFlox/Flox mice was confirmed by hematoxylin and eosin (HE) staining of lung sections. Further, immunohistochemical analysis of differential biomarkers suggested that these tumors correspond to lung adenocarcinomas. Taken together, our study demonstrate a promoting role of ERK3 in lung tumor formation in vivo. Advisors/Committee Members: Long, Weiwen (Advisor).

Subjects/Keywords: Biomedical Research; Biochemistry; ERK3; lung tumor; MAPK

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APA (6^th Edition):

Vallabhaneni, S. (2018). Investigating the Function of ERK3 In Lung Tumor Progression. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1526077960269769

Chicago Manual of Style (16^th Edition):

Vallabhaneni, Sreeram. “Investigating the Function of ERK3 In Lung Tumor Progression.” 2018. Masters Thesis, Wright State University. Accessed November 20, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1526077960269769.

MLA Handbook (7^th Edition):

Vallabhaneni, Sreeram. “Investigating the Function of ERK3 In Lung Tumor Progression.” 2018. Web. 20 Nov 2019.

Vancouver:

Vallabhaneni S. Investigating the Function of ERK3 In Lung Tumor Progression. [Internet] [Masters thesis]. Wright State University; 2018. [cited 2019 Nov 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1526077960269769.

Council of Science Editors:

Vallabhaneni S. Investigating the Function of ERK3 In Lung Tumor Progression. [Masters Thesis]. Wright State University; 2018. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1526077960269769

KTH

20. Nenchev, Vladislav. Robustness Analysis of MAPK Signaling Cascades.

Degree: Automatic Control, 2009, KTH

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106223

► The MAPK cascade is responsible for transmitting information in the cytoplasm of the cell and regulating important fate decisions like cell division and apoptosis.… (more)

▼ The MAPK cascade is responsible for transmitting information in the cytoplasm of the cell and regulating important fate decisions like cell division and apoptosis. Due to scarce experimental data and limited knowledge about many complex biochemical processes, existing MAPK pathway models, which exhibit bistability, have a significant structural uncertainty. Often, small perturbations of network interactions or components can reduce the bistable region significantly or make it even disappear and small fluctuations of the input can make the system switch back, which reflects its low robustness. However, real biological systems have developed significant robustness through evolution and this robustness should be reflected by the models. The main goal of the present thesis is the development of a methodology for increasing the robustness of biochemical models, which exhibit bistability. Based on modifying existing network interactions or introducing new interactions to the system, several methods for both internal and external robustification are proposed. Internal robustness is addressed through a sensitivity analysis, which deals with a linearization of the model and can be used sequentially to introduce multiple modifications to the model. The methods for external robustness improvement are based on eigenvalue placement and slope modification (drawing on the linear model) and on the identification of feedback structures (nonlinear model). Further, a way to integrate static interaction changes to the nonlinear model, so that these perturbations have only a local impact on its behavior, is proposed. The application of the methods to existing MAPK models shows that, by introducing small modifications, the internal and external robustness of models can be increased significantly and thus provides knowledge about complex dynamics and interactions that play a key role for the inherent robustness of real biological systems. Furthermore, by employing a robustness analysis, stable steady-state branches can be recovered and bistability can be induced.

Subjects/Keywords: robustness analysis; robustification; bistability; MAPK; biochemical

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APA (6^th Edition):

Nenchev, V. (2009). Robustness Analysis of MAPK Signaling Cascades. (Thesis). KTH. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106223

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nenchev, Vladislav. “Robustness Analysis of MAPK Signaling Cascades.” 2009. Thesis, KTH. Accessed November 20, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106223.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nenchev, Vladislav. “Robustness Analysis of MAPK Signaling Cascades.” 2009. Web. 20 Nov 2019.

Vancouver:

Nenchev V. Robustness Analysis of MAPK Signaling Cascades. [Internet] [Thesis]. KTH; 2009. [cited 2019 Nov 20]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106223.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nenchev V. Robustness Analysis of MAPK Signaling Cascades. [Thesis]. KTH; 2009. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106223

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of South Florida

21. Wu, Jheng-Yu. Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6.

Degree: 2017, University of South Florida

URL: https://scholarcommons.usf.edu/etd/6985

► Extracellular signal-regulated kinases 1/2 (ERK1/2) are important kinases regulating cell proliferation and cell migration, and have been established as therapeutic targets for cancer treatment. Previously,… (more)

Subjects/Keywords: acetylation; MAPK; PTM; inhibitor; Biochemistry; Cell Biology

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APA (6^th Edition):

Wu, J. (2017). Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/6985

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wu, Jheng-Yu. “Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6.” 2017. Thesis, University of South Florida. Accessed November 20, 2019. https://scholarcommons.usf.edu/etd/6985.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wu, Jheng-Yu. “Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6.” 2017. Web. 20 Nov 2019.

Vancouver:

Wu J. Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6. [Internet] [Thesis]. University of South Florida; 2017. [cited 2019 Nov 20]. Available from: https://scholarcommons.usf.edu/etd/6985.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wu J. Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6. [Thesis]. University of South Florida; 2017. Available from: https://scholarcommons.usf.edu/etd/6985

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

George Mason University

22. Voss, Kelsey. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .

Degree: 2014, George Mason University

URL: http://hdl.handle.net/1920/9093

► New World alphaviruses belonging to the family Togaviridae are known to infect humans and equines and cause encephalitic disease. The New World alphaviruses are classified… (more)

Subjects/Keywords: alphaviruses; host kinase; ERK; MAPK signalling; antiviral

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APA (6^th Edition):

Voss, K. (2014). Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . (Thesis). George Mason University. Retrieved from http://hdl.handle.net/1920/9093

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Voss, Kelsey. “Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .” 2014. Thesis, George Mason University. Accessed November 20, 2019. http://hdl.handle.net/1920/9093.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Voss, Kelsey. “Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .” 2014. Web. 20 Nov 2019.

Vancouver:

Voss K. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . [Internet] [Thesis]. George Mason University; 2014. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/1920/9093.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Voss K. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . [Thesis]. George Mason University; 2014. Available from: http://hdl.handle.net/1920/9093

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

23. Goettel, Jeremy Allen. Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production.

Degree: PhD, Cell and Developmental Biology, 2010, Vanderbilt University

URL: http://etd.library.vanderbilt.edu/available/etd-08032010-133210/ ;

► One Immunological disorders of the gastrointestinal tract is inflammatory bowel disease (IBD). IBD results in recurrent and persistently elevated levels of cytokines, such as tumor… (more)

▼ One Immunological disorders of the gastrointestinal tract is inflammatory bowel disease (IBD). IBD results in recurrent and persistently elevated levels of cytokines, such as tumor necrosis factor (TNF). TNF promotes activation of the mitogen-activated protein kinase (MAPK) pathway that consists of protein kinases Raf/MEK/ERK. Kinase suppressor of Ras-1 (KSR1) binds all three MAPK cascade components Raf, MEK and ERK to facilitate activation of this pathway. While KSR1 possesses a protein kinase domain, mammalian KSR1 contains an arginine in place of an invariant lysine residue required for ATP binding. Thus evidence supporting a catalytic function of KSR1 remains controversial. Using a recombinant protein expression system in bacteria, we demonstrated that KSR1 is a functional protein kinase that undergoes serine autophosphorylation and is phosphorylates recombinant kinase-inactive MEK1 (rMEK1 K97M). In addition, immunoprecipitated FLAG-tagged wild-type KSR1 expressed in KSR1-/- cells also phosphorylated rMEK1 K97M. Finally, KSR1 promoted colon epithelial cell survival in response to TNF that was dependent on a functional KSR1 kinase domain and MEK kinase activity in vitro. Since TNF is upregulated in human IBD, we studied the role of KSR1 during chronic inflammation by crossing KSR1-/- mice with the interleukin-10 deficient (Il10-/-) mouse model of spontaneous experimental colitis. KSR1-/-Il10-/- mice developed an accelerated severe colitis by 4 weeks of age. We determined that KSR1 expression in hematopoietic lineages mediated significant protection against colitis in Il10-/- mice. Further analysis indicated that naÃ¯ve CD4+ T cells lacking KSR1 produced higher levels of IFN-γ and had a greater propensity to differentiate along the Th1 axis. Finally, administration of neutralizing antibody against IFN-γ attenuated the disease in KSR1-/-Il10-/- mice. In summary, we have demonstrated that KSR1 is a functional protein kinase, MEK1 is an in vitro substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF. In addition, KSR1 suppresses colitis in Il10-/- mice by regulating IFN-γ production in CD4+ T cells and promotes effector T cell developmental homeostasis. These findings indicate that KSR1 is an important molecule involved in both epithelial cell survival and immune regulation. Therefore, further investigations utilizing agents that modulate KSR1 expression to suppress inflammation may validate KSR1 as a therapeutic target for patients with IBD. Advisors/Committee Members: Matthew J. Tyska (committee member), Roy Zent (committee member), Stephen R. Hann (committee member), D. Brent Polk (committee member), Steven K. Hanks (chair).

Subjects/Keywords: MAPK; KSR1; IFN; Colitis; IL-10; Kinase

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APA (6^th Edition):

Goettel, J. A. (2010). Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-08032010-133210/ ;

Chicago Manual of Style (16^th Edition):

Goettel, Jeremy Allen. “Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production.” 2010. Doctoral Dissertation, Vanderbilt University. Accessed November 20, 2019. http://etd.library.vanderbilt.edu/available/etd-08032010-133210/ ;.

MLA Handbook (7^th Edition):

Goettel, Jeremy Allen. “Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production.” 2010. Web. 20 Nov 2019.

Vancouver:

Goettel JA. Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production. [Internet] [Doctoral dissertation]. Vanderbilt University; 2010. [cited 2019 Nov 20]. Available from: http://etd.library.vanderbilt.edu/available/etd-08032010-133210/ ;.

Council of Science Editors:

Goettel JA. Kinase suppressor of Ras 1 is a functional protein kinase and protects from experimental colitis in mice by regulating T lymphocyte IFN-γ production. [Doctoral Dissertation]. Vanderbilt University; 2010. Available from: http://etd.library.vanderbilt.edu/available/etd-08032010-133210/ ;

Duquesne University

24. Monlish, Darlene A. Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors.

Degree: PhD, Pharmacology-Toxicology, 2013, Duquesne University

URL: https://dsc.duq.edu/etd/941

► Age remains the most common demographic risk factor in breast cancer. The underlying cellular signaling mechanisms responsible for the age-associated rise in disease incidence have… (more)

▼ Age remains the most common demographic risk factor in breast cancer. The underlying cellular signaling mechanisms responsible for the age-associated rise in disease incidence have not yet been determined. Studies presented herein aim to elucidate age-related changes in the extracellular signal-regulated kinases, ERK1/2 and ERK5, of the mitogen-activated protein kinase (MAPK) pathway, and in the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway. Further, the role of the MEK5-ERK5 cascade in breast cancer cell proliferation, migration, and invasion was analyzed. In addition, several series of novel MEK5 inhibitors were characterized with regard to both efficacy and selectivity. In vitro assessment revealed distinct patterns of kinase expression and activation among the three breast cancer cell lines evaluated. In a spontaneous model of breast cancer, the expression and activation of ERK5 increased with age in tumor tissue, while no changes were observed in adjacent normal mammary tissue. Pharmacological inhibition of ERK5 decreased cell migration and invasion in a cellular model of triple-negative breast cancer. In addition, studies involving single and dual delivery of kinase inhibitors further promote targeting ERK5 in breast cancer due to its role in the upregulation of the related ERK1/2 and Akt pathways and suggest ERK5 exhibits specialized patterns of activation with regard to distinct tumor subtypes. The patterns of expression strongly indicate the need for individual tailoring of pharmaceutical interventions based on patient hormonal status and age and suggest the important role of the novel protein kinase, ERK5, in cell invasion and migration. The characterization of a series of diphenyl aniline compounds revealed a putative MEK5 inhibitor capable of reducing cell growth and reverting the epithelial-to-mesenchymal transition in triple-negative breast cancer cells. Full characterization of the MEK5-ERK5 cascade in breast cancer will assist in the development of more targeted inhibitors, thereby reducing toxicity and increasing efficacy in select patient cohorts. Advisors/Committee Members: Jane Cavanaugh, Melanie Flint, Lauren O'Donnell, Wilson Meng, Paula Witt-Enderby.

Subjects/Keywords: Age; Breast Cancer; ERK5; Inhibitors; MAPK; PI3K

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APA (6^th Edition):

Monlish, D. A. (2013). Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors. (Doctoral Dissertation). Duquesne University. Retrieved from https://dsc.duq.edu/etd/941

Chicago Manual of Style (16^th Edition):

Monlish, Darlene A. “Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors.” 2013. Doctoral Dissertation, Duquesne University. Accessed November 20, 2019. https://dsc.duq.edu/etd/941.

MLA Handbook (7^th Edition):

Monlish, Darlene A. “Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors.” 2013. Web. 20 Nov 2019.

Vancouver:

Monlish DA. Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors. [Internet] [Doctoral dissertation]. Duquesne University; 2013. [cited 2019 Nov 20]. Available from: https://dsc.duq.edu/etd/941.

Council of Science Editors:

Monlish DA. Age-Related Effects on the Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Pathways in Breast Cancer and the Characterization of Novel MEK5 Inhibitors. [Doctoral Dissertation]. Duquesne University; 2013. Available from: https://dsc.duq.edu/etd/941

University of Newcastle

25. Ewen, Katherine. Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development.

Degree: PhD, 2010, University of Newcastle

URL: http://hdl.handle.net/1959.13/807499

►

Research Doctorate - Doctor of Philosophy (PhD)

In the fields of sex determination, embryonic gonad development and germ cell differentiation, much effort has been placed… (more)

▼

Research Doctorate - Doctor of Philosophy (PhD)

In the fields of sex determination, embryonic gonad development and germ cell differentiation, much effort has been placed in performing large-scale screens anchored in RNA and DNA technologies. Whilst these technologies have identified new candidate genes, they are unable to provide expression data for functionally active gene products. Recent improvements in the sensitivity of proteomic screening technologies have made analysis of the embryonic gonadal proteome experimentally feasible. Thus, major aims of my PhD were to generate a data set of gonadal proteins expressed at the time of sex determination, and to identify differentially expressed proteins that potentially regulate early events in gonadogenesis, germ cell development and sex differentiation. To detect and identify gonadal proteins, I used two-dimensional nano-flow liquid chromatography and tandem mass spectrometry. I identified 1037 proteins which primarily serve in RNA post-transcriptional modification and trafficking, protein synthesis and folding, and post-translational modification. Over 300 proteins were not identified in a similar transcriptomic study. Over 60 proteins were identified with potential links to human disorders of sexual development (DSDs). I identified four proteins up-regulated in the ovary and three proteins up-regulated in the testis at a critical time point in sex determination. I also identified five proteins increasing, and three proteins decreasing, in expression during early testis development. Two of these temporally-regulated proteins are associated with human DSDs. The majority of these expression differences have not been detected at the transcript level. These data provide novel targets potentially controlling events in gonadogenesis, sex determination and germ cell differentiation. Recently, the field of germ cell sex differentiation was revolutionised with the discovery that retinoic acid (RA) initiates meiosis in female embryonic germ cells, and that the RA-degrading enzyme CYP26B1 inhibits meiosis in male germ cells, which consequently cease mitotic division till after birth. How these somatic environmental factors regulate the transition from mitosis to meiosis or mitotic arrest remains unanswered. p38 MAP kinase (MAPK) signalling initiates mitotic arrest in other differentiating cell types. Thus, a specific aim of my PhD was to investigate the role of p38 MAPK in controlling male germ cell differentiation. To address this aim experimentally, I analysed expression of p38 MAPK in embryonic gonads and found it to be activated in differentiating male germ cells. I then blocked p38 MAPK signalling and found that male germ cells expressed pluripotency and meiosis-associated proteins in a similar pattern to their female counterparts, and that testes exhibited more meiotic germ cells. These data suggest that p38 MAPK signalling contributes to meiosis inhibition in testicular germ cells, and potentially directs them towards quiescence. The studies outlined in this thesis…

Advisors/Committee Members: University of Newcastle. Faculty of Science and Information Technology, School of Environmental and Life Sciences.

Subjects/Keywords: gonad; germ cell; proteomic; p38 MAPK

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APA (6^th Edition):

Ewen, K. (2010). Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/807499

Chicago Manual of Style (16^th Edition):

Ewen, Katherine. “Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development.” 2010. Doctoral Dissertation, University of Newcastle. Accessed November 20, 2019. http://hdl.handle.net/1959.13/807499.

MLA Handbook (7^th Edition):

Ewen, Katherine. “Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development.” 2010. Web. 20 Nov 2019.

Vancouver:

Ewen K. Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development. [Internet] [Doctoral dissertation]. University of Newcastle; 2010. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/1959.13/807499.

Council of Science Editors:

Ewen K. Large-scale proteomic screen and signal transduction analysis used to study embryonic gonad and germ cell development. [Doctoral Dissertation]. University of Newcastle; 2010. Available from: http://hdl.handle.net/1959.13/807499

University of New South Wales

26. Huang, Yizhou. Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells.

Degree: Prince of Wales Medical Research Institute, 2015, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/55310 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37094/SOURCE02?view=true

► Direct modulation of oncogenic transcriptional programs by targeting aberrantly regulated transcription factors is a promising area of research for cancer treatment. The ETS factor ERG… (more)

▼ Direct modulation of oncogenic transcriptional programs by targeting aberrantly regulated transcription factors is a promising area of research for cancer treatment. The ETS factor ERG (ETS-related gene) plays an important role in haematopoiesis and is also a potent oncoprotein with leukaemogenic activity in mouse models. In humans, high ERG expression is associated with poor patient outcomes in acute myeloid leukaemia (AML) and T-cell acute lymphoblastic leukaemia (T-ALL). However, gaps still exist in our knowledge regarding the post-translational regulation of ERG. Protein phosphorylation is known to regulate the transcriptional activity of many ETS factors. Yet, as a known phosphoprotein, how ERG activity responds to phosphorylating signalling pathways that are associated with the onset and progression of leukaemia is largely unknown.To unravel the post-translational regulation of ERG, I used liquid chromatography coupled tandem mass spectrometry to identify five phosphorylated serines (S) (S55, S88, S103, S222, S283) on endogenous ERG immunoprecipitated from MOLT-4 T-ALL cells with S283 phosphorylation (pS283) strongly enriched in leukaemic cells compared with healthy haematopoietic stem/progenitor cells (HSPCs). Generation of a customised anti-ERG pS283 antibody to probe upstream signalling pathways in primary ALL and AML xenografts identifies early T-cell precursor ALL cells with poor prognosis to exhibit particularly high levels of pS283, and there was a direct association between levels of pS283 and active extracellular signal-regulated kinase (ERK). Over-expression of phosphomimetic ERG mutant (S283D) enhanced the expansion and clonogenicity of transduced primary HSPCs more than wild-type (WT) ERG. This phenotype was associated with induction of genes involved in mitogen-activated protein kinase (MAPK)/ERK signalling. Further experiments showed ERG pS283 was directly modulated by ERK, consistent with the existence of a positive feedback loop that stabilised this modification in leukaemic cells. There were no substantial differences between WT and mutant ERG with regards to protein stability, nuclear transfer or direct DNA binding, however, there was increased enrichment of S283D ERG at specific leukaemia-associated enhancers.This work significantly expands existing knowledge of ERG phosphorylation in leukaemic cells and identifies a specific modification that could be targeted to modulate ERG-driven leukaemic transcriptional programs. Advisors/Committee Members: Pimanda, John, Prince of Wales Medical Research Institute, Faculty of Medicine, UNSW, Wong, Jason, Prince of Wales Medical Research Institute, Faculty of Medicine, UNSW.

Subjects/Keywords: Haematopoiesis; ERG; Leukaemia; Transcription factor; Phosphorylation; MAPK

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APA (6^th Edition):

Huang, Y. (2015). Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/55310 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37094/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Huang, Yizhou. “Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells.” 2015. Doctoral Dissertation, University of New South Wales. Accessed November 20, 2019. http://handle.unsw.edu.au/1959.4/55310 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37094/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Huang, Yizhou. “Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells.” 2015. Web. 20 Nov 2019.

Vancouver:

Huang Y. Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells. [Internet] [Doctoral dissertation]. University of New South Wales; 2015. [cited 2019 Nov 20]. Available from: http://handle.unsw.edu.au/1959.4/55310 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37094/SOURCE02?view=true.

Council of Science Editors:

Huang Y. Characterisation of functional validation of ERG phosphorylation in normal haematopoietic and leukaemic cells. [Doctoral Dissertation]. University of New South Wales; 2015. Available from: http://handle.unsw.edu.au/1959.4/55310 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:37094/SOURCE02?view=true

Colorado State University

27. Herman, Jacob A. Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects.

Degree: PhD, Biochemistry and Molecular Biology, 2015, Colorado State University

URL: http://hdl.handle.net/10217/166957

► Kinetochores, large protein structures assembled on centromeric DNA during mitosis, bind to microtubules of the mitotic spindle to orchestrate and power chromosome movements. Deregulation of… (more)

▼ Kinetochores, large protein structures assembled on centromeric DNA during mitosis, bind to microtubules of the mitotic spindle to orchestrate and power chromosome movements. Deregulation of kinetochore-microtubule (kinetochore-MT) attachments has been implicated in driving chromosome instability and cancer evolution; however, the nature and source of kinetochore-MT attachment defects in cancer cells remain largely unknown. Here, we identify kinetochore-MT attachments, and their regulation by Aurora B kinase (ABK) as key targets for selective therapeutic intervention in glioblastoma and other cancers. We observe that accessory regulators of ABK and kinetochore-microtubule attachment stability are compromised in some cancers and fundamentally alter kinetochore signaling. First we identify RAS/MAPK oncogenic transformation as sufficient to induce these defects through an enzymatic cascade targeting the kinetochore. We then identify BUBR1 kinetochore recruitment and kinetochore-associated PP2A activity as cancer-essential activities, which are required for some cancers to form robust physical interactions between kinetochores and MTs. We also verify previous findings that many cancers are characterized by chromosome segregation errors arising from merotelic kinetochore-microtubule attachments (a single kinetochore bound to microtubules emanating from both spindle poles). We attribute the cause of these errors to be a decrease in MT dynamics independent of the physical attachments status. Finally we characterize a novel kinetochore component, BUGZ, which serves as a molecular chaperone for BUB3 and thus indirectly stimulates ABK activity. We find that BUGZ binds to BUB3 through a conserved GLEBS domain, and this interaction is required for BUB3 kinetochore localization. BUGZ depletion decreases ABK activity resulting in lethal chromosome alignment defects in glioblastoma cells and genetically transformed cells. Together these findings further elucidate the molecular mechanism by which kinetochore-MT attachments are regulated and importantly, how this mechanism is perturbed upon transformation. These results will make the design and application of novel anti-cancer drugs with reduced side effects possible because the specifically target cancer populations. Advisors/Committee Members: DeLuca, Jenniver G. (advisor), Bamburg, James (committee member), Stargell, Laurie (committee member), Nickoloff, Jac (committee member).

Subjects/Keywords: BubR1; MAPK; RAS; Kinetochore; Aurora B; PP2A

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APA (6^th Edition):

Herman, J. A. (2015). Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/166957

Chicago Manual of Style (16^th Edition):

Herman, Jacob A. “Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects.” 2015. Doctoral Dissertation, Colorado State University. Accessed November 20, 2019. http://hdl.handle.net/10217/166957.

MLA Handbook (7^th Edition):

Herman, Jacob A. “Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects.” 2015. Web. 20 Nov 2019.

Vancouver:

Herman JA. Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects. [Internet] [Doctoral dissertation]. Colorado State University; 2015. [cited 2019 Nov 20]. Available from: http://hdl.handle.net/10217/166957.

Council of Science Editors:

Herman JA. Investigation of the molecular mechanisms and therapeutic potential of oncogene-induced kinetochore-microtubule defects. [Doctoral Dissertation]. Colorado State University; 2015. Available from: http://hdl.handle.net/10217/166957

28. Vincent, Laure-Anaïs. Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors.

Degree: Docteur es, Biologie Santé, 2014, Université Montpellier I

URL: http://www.theses.fr/2014MON13523

► Le mélanome malin (MM) métastatique, un des cancers les plus intrinsèquement résistants aux agents anti-cancéreux et présentant une forte capacité à développer des résistances acquises,… (more)

▼ Le mélanome malin (MM) métastatique, un des cancers les plus intrinsèquement résistants aux agents anti-cancéreux et présentant une forte capacité à développer des résistances acquises, constitue un défi thérapeutique. La meilleure compréhension des mécanismes impliqués dans cette chimiorésistance permettrait d'identifier des cibles thérapeutiques ou de guider le choix du traitement pour une meilleure efficacité. Les travaux réalisés durant cette thèse se sont focalisés sur l'identification de nouveaux déterminants moléculaires de la résistance acquise du MM vis-à-vis (i) des vinca-alcaloïdes (VAs, chimiothérapie classique), (ii) des inhibiteurs de MAP kinases (iMAPK, thérapie ciblée). Pour la première étude, un modèle de lignées cellulaires de MM résistantes aux VAs (CAL1R-VAs) a été établi (exposition continue, 12 mois, de la lignée parentale CAL1-wt à la VCR, la VDS ou la VRB : CAL1R-VCR, CAL1R-VDS et CAL1R-VRB respectivement). La comparaison des profils d'expression a permis de distinguer deux groupes de lignées cellulaires (CAL1R-VCR et CAL1R-VDS ; CAL1R-VRB et CAL1-wt), suggérant une résistance différentielle du MM aux VAs : d'une part à la VCR et à la VDS, d'autre part à la VRB. L'analyse des données transcriptomiques par une démarche associant successivement trois méthodes - RMA (Robust Multi-array Average), RDAM (Rank Difference Analysis of Microarrays) et MGSA (model-based gene set analysis) – a permis d'identifier des fonctions cellulaires altérées lors de la sélection des lignées CAL1R-VAs, et donc potentiellement à l'origine de la résistance de ces lignées. Des analyses fonctionnelles in vitro ont permis de confirmer l'implication des lysosomes et de la réponse au stress du réticulum endoplasmique (RE) dans la résistance différentielle des cellules CAL1 aux VAs. Ainsi, une sous-expression des cathepsines B et L (bioinformatique) et une réduction du volume du compartiment acide (in vitro) ont été observées spécifiquement dans le premier groupe de lignées (CAL1R-VCR et CAL1R-VDS), suggérant une sensibilité réduite de ces lignées à la voie lysosomale de l'apoptose. Par ailleurs, l'inhibition de la voie de réponse au stress du RE par l'acide tauroursodésoxycholique (TUDCA) a induit une sensibilisation différentielle de l'ensemble des lignées CAL1 aux VAs, suggérant l'implication de cette voie dans la résistance différentielle primaire et acquise aux VAs. De plus, l'inhibition de la réponse au stress du RE a induit une sensibilisation d'une autre lignée cellulaire de MM, MDA-MB-435, à la VCR et à la VDS mais pas à la VRB. Ainsi, la voie de réponse au stress du RE semble impliquée dans la résistance différentielle du MM aux VAs. Ce mécanisme pourrait mettre en jeu l'autophagie, dont le flux était significativement augmenté dans le premier groupe de lignées. La même démarche d'analyse transcriptomique a été appliquée pour l'étude des mécanismes moléculaires de résistance acquise du MM aux iMAPK. Des lignées cellulaires de MM résistantes aux trois iMAPK majeurs ont été établies par exposition continue de la… Advisors/Committee Members: Cuq, Pierre (thesis director).

Subjects/Keywords: Mélanome; Résistance; Transcriptome; Vinca-Alcaloïdes; Mapk; Braf; Melanoma; Resistance; Microarray; Vinca-Alkaloids; Mapk; Braf; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vincent, L. (2014). Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2014MON13523

Chicago Manual of Style (16^th Edition):

Vincent, Laure-Anaïs. “Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors.” 2014. Doctoral Dissertation, Université Montpellier I. Accessed November 20, 2019. http://www.theses.fr/2014MON13523.

MLA Handbook (7^th Edition):

Vincent, Laure-Anaïs. “Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors.” 2014. Web. 20 Nov 2019.

Vancouver:

Vincent L. Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors. [Internet] [Doctoral dissertation]. Université Montpellier I; 2014. [cited 2019 Nov 20]. Available from: http://www.theses.fr/2014MON13523.

Council of Science Editors:

Vincent L. Etude des mécanismes moléculaires de chimiorésistance du mélanome malin aux vinca-alcaloïdes et aux inhibiteurs de kinases par une approche transcriptomique : Molecular study of melanoma chemoresistance to vinca-alkaloids and MAP Kinase inhibitors. [Doctoral Dissertation]. Université Montpellier I; 2014. Available from: http://www.theses.fr/2014MON13523

Universidade Federal de Santa Maria

29. Mariane Trindade de Paula. ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster.

Degree: 2012, Universidade Federal de Santa Maria

URL: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4485

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O Mercúrio (Hg) é em um metal pesado de relevância toxicológica cuja contaminação ambiental decorre principalmente de atividades antropogênicas. Dentre os mecanismos moleculares envolvidos na… (more)

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O Mercúrio (Hg) é em um metal pesado de relevância toxicológica cuja contaminação ambiental decorre principalmente de atividades antropogênicas. Dentre os mecanismos moleculares envolvidos na toxicidade do Hg estão um aumento na produção de espécies reativas de oxigênio, diminuição na atividade de enzimas antioxidantes e modulação da fosforilação de proteínas que participam de vias de transdução de sinal celular, entre estas as Proteínas Cinases Ativadas por Mitógenos (MAPKs). Estudos apontam Drosophila melanogaster como um organismo que apresenta um considerável potencial para atuar como um bioindicador de contaminantes ambientais, apresentando alterações bioquímicas e comportamentais similares a efeitos observados em mamíferos. Deste modo, nossos resultados demonstraram que o HgCl2, quando incorporado na dieta junto com sacarose em D. melanogaster, causa significativa diminuição da viabilidade das mesmas a partir de 24h de modo dependente de concentração utilizada do composto. Além disso, após 48h de exposição ao Hg(II) as moscas tratadas com concentrações a partir de 100μM obtiveram prejuízos no desempenho locomotor, diminuição na atividade das enzimas: Acetilcolinesterase (Ache), Glutationa Peroxidase (GPx) e Superóxido Dismutase (SOD), não alterando a atividade da Catalase (CAT). Na análise dos genes de D. melanogaster, através do método de Real time-PCR, observou-se que os níveis NF-E2-relacionados fator 2 (Nrf2) não foram alterados em comparação ao grupo controle, sendo que os níveis de HSP83 foram aumentados em 10 vezes. Além disso, a partir de 6h de tratamento as moscas demonstraram indução na peroxidação lipídica e estresse oxidativo efeito este que persistiu até as 48h de tratamento. Na medição dos níveis de Hg, expressa em μg de Hg/g de tecido, observou-se que as moscas tratadas por 48h com HgCl2 apresentaram 100 vezes maiores níveis de Hg em comparação ao grupo controle. Com relação à análise da modulação de MAPKs pelo tratamento com HgCl2 observou-se aumentada fosforilação de JNK e ERK, sem alterar a fosforilação de p38MAPK, bem como o conteúdo total destas proteínas. HgCl2 levou a uma elevação na clivagem da proteína PARP, indicativo da indução de morte celular do tipo apoptótica. Os dados obtidos neste trabalho ressaltam a toxicidade do Hg(II) e estendem o conhecimento sobre seus mecanismos de ação para um modelo animal de invertebrado, além disso, o presente estudo aponta o sistema antioxidante e vias de transdução de sinal celular como mecanismos comuns envolvidos na toxicidade deste metal em vertebrados e invertebrados..

Mercury (Hg) consists in a heavy metal with toxicological relevance whose contamination is mainly attributed to anthropogenic activities, leading to environmental contamination. It is known that an induction in oxidative stress caused by increased production of reactive oxygen species and/or decrease in antioxidant enzymes activity and a modulation of phosphorylation of proteins that participate in processes of cellular signaling transduction, as Mitogen-Activated…

Advisors/Committee Members: Caroline Wagner, Thais Posser, Jeferson Luis Franco.

Subjects/Keywords: Estresse Oxidativo; MAPK; Drosophila melanogaster; Mercúrio; CIENCIAS BIOLOGICAS; Mercury; Drosophila melanogaster; MAPK; Oxidative Stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Paula, M. T. d. (2012). ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster. (Thesis). Universidade Federal de Santa Maria. Retrieved from http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4485

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Paula, Mariane Trindade de. “ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster.” 2012. Thesis, Universidade Federal de Santa Maria. Accessed November 20, 2019. http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4485.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Paula, Mariane Trindade de. “ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster.” 2012. Web. 20 Nov 2019.

Vancouver:

Paula MTd. ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster. [Internet] [Thesis]. Universidade Federal de Santa Maria; 2012. [cited 2019 Nov 20]. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4485.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Paula MTd. ESTUDO DAS ALTERAÇÕES COMPORTAMENTAIS E BIOQUÍMICAS INDUZIDAS PELA EXPOSIÇÃO AO Hg (II) SOBRE O SISTEMA ANTIOXIDANTE E VIAS DE SINALIZAÇÃO CELULAR EM Drosophila melanogaster. [Thesis]. Universidade Federal de Santa Maria; 2012. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4485

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Federal de Santa Maria

30. Bernardo Garziera Gasperin. REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR.

Degree: 2012, Universidade Federal de Santa Maria

URL: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4885

► O controle local da seleção folicular em mamíferos ainda é pouco compreendido. O objetivo do presente estudo foi identificar fatores locais, receptores e rotas de… (more)

▼ O controle local da seleção folicular em mamíferos ainda é pouco compreendido. O objetivo do presente estudo foi identificar fatores locais, receptores e rotas de sinalização envolvidas na seleção do folículo dominante e atresia dos subordinados em bovinos. Em um primeiro estudo, avaliou-se a regulação e função do FGF10 e do seu receptor FGFR2b durante a divergência folicular. A expressão de FGF10 e FGFR2b foi significativamente maior nas células da teca e granulosa, respectivamente, provenientes dos folículos subordinados. A injeção intrafolicular de FGF10 inibiu o crescimento folicular de maneira dose dependente e reduziu significativamente a síntese de estradiol. Nas células da granulosa, a injeção de FGF10 diminuiu a expressão de RNAm de CYP19A1 e ciclina D2, enquanto que uma tendência de aumento da expressão do receptor FGFR2b foi observada. Nas células da teca, um aumento significativo na expressão de FGF10 foi observado nos folículos tratados com FGF10. Em um segundo estudo, o padrão de expressão dos receptores de BMPs e das proteínas BMP15 e GDF9 foram avaliados em vacas ovariectomizadas em diferenes dias em relação ao inicio da onda folicular, comparando os dois maiores folículos antes (dia 2), durante (dia 3) ou após a divergência folícular (dia 4). No dia 2 da onda folicular, foi observada maior expressão do receptor BMPR-1A e tendências a maior expressão dos receptores BMPR-2 e -1B nos futuros folículos subordinados. No dia 3, quando os folículos dominantes e subordinados são identificados, a expressão de BMPR-1B e -2 foi maior nos folículos subordinados. No dia 4, o receptor BMPR1B (RNAm e proteína) foi significativamente mais expresso nas células da granulosa de folículos atrésicos. O aumento da expressão do BMPR1B durante a atresia folicular foi confirmado nas células da granulosa de folículos induzidos à atresia através do tratamento com FGF10 ou inibidor dos receptores de estradiol. A abundância de BMP15 e GDF9 no fluído folicular não diferiu entre folículos dominantes e subordinados. Em um terceiro estudo, buscou-se identificar rotas de sinalização diferentemente ativas nas células da granulosa durante a divergência. Os níveis de MAPK fosforilada foram significativamente superiores nos futuros folículos dominantes (dia 2), mas não diferiram entre os dois maiores folículos durante ou após a divergência. Folículos subordinados apresentaram maiores níveis de STAT3 fosforilada em relação aos seus respectivos dominantes em todos os pares de folículos coletados, sendo observado um aumento significativo em folículos atrésicos coletados no dia 4. Em conclusão, os resultados sugerem que a expressão reduzida de FGF10 e do receptor FGFR2b possibilitam o crescimento e diferenciação do folículo dominante, enquanto que o aumento da sinalização do FGF10 no folículo subordinado está associado com a atresia. O perfil de expressão dos receptores BMPR-2, -1B e -1A indica que os mesmos apresentam funções na regulação da divergência folicular em bovinos. A fosforilação da MAPK é um marcador inicial de dominância… Advisors/Committee Members: William Schoenau, Fabio Vasconcellos Comim, Luís Fabiano Santos da Costa, Fernando Silveira Mesquita, Paulo Bayard Dias Goncalves.

Subjects/Keywords: STAT3; MAPK; BMP15; GDF9; BMPRs; FGF10; MEDICINA VETERINARIA; BMP15; GDF9; BMPRs; FGF10; MAPK; STAT3

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gasperin, B. G. (2012). REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR. (Thesis). Universidade Federal de Santa Maria. Retrieved from http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gasperin, Bernardo Garziera. “REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR.” 2012. Thesis, Universidade Federal de Santa Maria. Accessed November 20, 2019. http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gasperin, Bernardo Garziera. “REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR.” 2012. Web. 20 Nov 2019.

Vancouver:

Gasperin BG. REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR. [Internet] [Thesis]. Universidade Federal de Santa Maria; 2012. [cited 2019 Nov 20]. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gasperin BG. REGULAÇÃO DA DIVERGÊNCIA FOLICULAR IN VIVO: UMA ABORDAGEM MOLECULAR. [Thesis]. Universidade Federal de Santa Maria; 2012. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=4885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations