subject:(MAPK)

Universidad de Cantabria

1. Herrero Mier, Ana. Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas.

Degree: 2013, Universidad de Cantabria

► La cascada de señalización de ERK(Extracellular-Signal-Regulated Kinase) es una ruta formada por proteínas quinasas activadas por mitógenos (MAPKs) que regula una amplia variedad de procesos… (more)

Subjects/Keywords: MAPK

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Herrero Mier, A. (2013). Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas. (Doctoral Dissertation). Universidad de Cantabria. Retrieved from http://hdl.handle.net/10902/1886

Chicago Manual of Style (16^th Edition):

Herrero Mier, Ana. “Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas.” 2013. Doctoral Dissertation, Universidad de Cantabria. Accessed March 07, 2021. http://hdl.handle.net/10902/1886.

MLA Handbook (7^th Edition):

Herrero Mier, Ana. “Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas.” 2013. Web. 07 Mar 2021.

Vancouver:

Herrero Mier A. Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas. [Internet] [Doctoral dissertation]. Universidad de Cantabria; 2013. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10902/1886.

Council of Science Editors:

Herrero Mier A. Especifidad espacio temporal de las señales Ras-ERK en la determinación de respuestas biológicas. [Doctoral Dissertation]. Universidad de Cantabria; 2013. Available from: http://hdl.handle.net/10902/1886

Wake Forest University

2. Collard, Marianne. MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER.

Degree: 2019, Wake Forest University

URL: http://hdl.handle.net/10339/94315

► Triple negative breast cancer (TNBC) is an aggressive subtype that comprises 12-17% of breast cancer cases. TNBC has a high propensity to metastasize; about one-third… (more)

Subjects/Keywords: mapk

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Collard, M. (2019). MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/94315

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):

Collard, Marianne. “MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER.” 2019. Thesis, Wake Forest University. Accessed March 07, 2021. http://hdl.handle.net/10339/94315.

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

MLA Handbook (7^th Edition):

Collard, Marianne. “MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER.” 2019. Web. 07 Mar 2021.

Vancouver:

Collard M. MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER. [Internet] [Thesis]. Wake Forest University; 2019. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10339/94315.

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

Council of Science Editors:

Collard M. MUSCADINE GRAPE EXTRACT AS A THERAPEUTIC FOR TRIPLE NEGATIVE BREAST CANCER. [Thesis]. Wake Forest University; 2019. Available from: http://hdl.handle.net/10339/94315

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

Texas A&M University

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

Degree: MS, Biology, 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

Record Details Similar Records Cite « Share

❌

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

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. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/157101

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. Masters Thesis, Texas A&M University. Accessed March 07, 2021. http://hdl.handle.net/1969.1/157101.

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. 07 Mar 2021.

Vancouver:

Jayant Kumar Ojha N. Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa. [Internet] [Masters thesis]. Texas A&M University; 2016. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1969.1/157101.

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. [Masters Thesis]. Texas A&M University; 2016. Available from: http://hdl.handle.net/1969.1/157101

4. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

Texas A&M University

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

Degree: PhD, Genetics, 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

Record Details Similar Records Cite « Share

❌

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. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/151390

Chicago Manual of Style (16^th Edition):

Goldsmith, Charles Sidney. “Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock.” 2013. Doctoral Dissertation, Texas A&M University. Accessed March 07, 2021. http://hdl.handle.net/1969.1/151390.

MLA Handbook (7^th Edition):

Goldsmith, Charles Sidney. “Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock.” 2013. Web. 07 Mar 2021.

Vancouver:

Goldsmith CS. Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock. [Internet] [Doctoral dissertation]. Texas A&M University; 2013. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1969.1/151390.

Council of Science Editors:

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

Penn State University

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

Degree: 2014, Penn State University

URL: https://submit-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. Advisors/Committee Members: Leonard Shelton Jefferson Jr., Thesis Advisor/Co-Advisor, Scot R Kimball, Thesis Advisor/Co-Advisor, Ralph Lauren Keil, Thesis Advisor/Co-Advisor.

Subjects/Keywords: MAPK signaling; muscle hypertrophy; tenotomy

Record Details Similar Records Cite « Share

❌

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 . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/20079

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):

Martin, Tony Dewayne. “An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading .” 2014. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/20079.

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

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. 07 Mar 2021.

Vancouver:

Martin TD. An Investigation of Kinases Responsible for Site-specific Phosphorylation of p70s6k1 in Skeletal Muscle Following Chronic Functional Overloading . [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/20079.

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

Council of Science Editors:

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

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

University of Ottawa

7. McDonell, Laura Marie. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .

Degree: 2018, University of Ottawa

URL: http://hdl.handle.net/10393/37610

► Ras-MAPK signalling regulates key cellular processes such as proliferation, differentiation and survival. Unsurprisingly, mutations in RAS genes are now recognized as potent oncogenic drivers. However,… (more)

▼ Ras-MAPK signalling regulates key cellular processes such as proliferation, differentiation and survival. Unsurprisingly, mutations in RAS genes are now recognized as potent oncogenic drivers. However, disruption of this pathway during development is associated with a family of disorders termed the Rasopathies. Shared clinical features include cutaneous, neurological and cardiac anomalies. At the outset of this study, the genetic etiology of three neurocutaneous disorders, microcephaly-capillary malformation syndrome (MIC-CAP), encephalocraniocutaneous lipomatosis (ECCL) and PHACE (Posterior fossa malformations, facial Hemangiomas, cerebral Arterial anomalies, Cardiovascular defects and Eye abnormalities) syndrome had not yet been established. This thesis identifies mutations in STAM-binding protein (STAMBP) in a cohort of individuals with MIC-CAP syndrome using whole-exome sequencing (WES). This gene encodes a deubiquitinating isopeptidase that regulates cell surface receptor-mediated endocytosis and sorting. Cell lines of individuals with MIC-CAP show reduced STAMBP expression, associated with accumulation of ubiquitinated protein aggregates, increased apoptosis and constitutive activation of the Ras-MAPK and PI3K-AKT pathways. WES also enabled the identification of post-zygotic mutations within the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1) in individuals with ECCL. Fibroblasts from affected individuals showed increased phosphorylation of the FGFRs consistent with receptor activation as well as insensitive signal transduction through the Ras-MAPK pathway. Neurocutaneous syndromes can feature striking vascular lesions such as the cerebral vasculopathy and large segmented facials hemangiomas seen in PHACE syndrome. The asymmetric and patchy vascular malformations coupled with a sporadic incidence and absence of familial recurrence suggested that PHACE might be caused by post-zygotic mutations. Interrogation of a discordant sib-pair using copy number analysis and WES did not identify causative mutations indicating the need for a comprehensive and targeted –omic approach to elucidate the molecular mechanism of this syndrome. Taken together, these findings expand the spectrum of the Rasopathies while providing novel pathomechanistic insights into the regulation of cellular proliferation and survival during development.

Subjects/Keywords: Ras-Mapk Signalling; Neurocutaneous Disorders

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

McDonell, L. M. (2018). Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/37610

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):

McDonell, Laura Marie. “Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .” 2018. Thesis, University of Ottawa. Accessed March 07, 2021. http://hdl.handle.net/10393/37610.

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

MLA Handbook (7^th Edition):

McDonell, Laura Marie. “Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders .” 2018. Web. 07 Mar 2021.

Vancouver:

McDonell LM. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . [Internet] [Thesis]. University of Ottawa; 2018. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10393/37610.

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

Council of Science Editors:

McDonell LM. Disruption of Ras-Mapk Signalling in Human Neurocutaneous Disorders . [Thesis]. University of Ottawa; 2018. Available from: http://hdl.handle.net/10393/37610

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

University College Cork

8. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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 Melbourne

9. Elsum, Imogen. Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble.

Degree: 2011, University of Melbourne

URL: http://hdl.handle.net/11343/36165

► Cancer is a complex disease with progression to a malignant phenotype requiring the cooperation of several transformation events. Cooperation between oncogene activation and loss of… (more)

▼ Cancer is a complex disease with progression to a malignant phenotype requiring the cooperation of several transformation events. Cooperation between oncogene activation and loss of polarity genes was first demonstrated in Drosophila melanogaster where flies expressing an activated Ras were screened for secondary mutations that led to metastatic growth. In this screen several polarity proteins were identified including Scribble, Discs Large (Dlg) and Lethal Giant Larvae (Lgl) (Pagliarini and Xu, 2003). Functional characterisation of Scribble showed it restricted tissue overgrowth, cell invasion and metastasis. A single mammalian homologue exists of the Drosophila Scribble and recent work has demonstrated that similarly to what is observed in Drosophila, in mammalian systems, loss of Scribble also cooperates with activated Ras to promote invasion. Here I have undertaken a detailed analysis of the mechanisms by which aberrant Scribble expression contributes to Ras dependent tumourigenesis. This question has been addressed in several ways. To assess how Scribble regulates transcriptional programmes, extensive microarray analysis was carried out from cells overexpressing or depleted of Scribble in the context of wildtype or activated Ras from both 2D and 3D cultures. Distinct gene signatures result depending on both the culture condition, and relative Scribble expression. Additionally, the cellular processes and pathways affected by altering Scribble expression differ depending on the contextual presence of wildtype or onogenic Ras, indicative of a multifaceted function for Scribble in regulating Ras transformation. In support of functional assays, strong antagonism is seen in the transcriptional response between cells overexpressing Scribble and those expressing oncogenic Ras. Furthermore, Scribble overexpression produces a cell adhesion signature that involves the upregulation of several tight junction components. A crucial role for Scribble in tight junction assembly was confirmed by demonstrating that Scribble promotes functional tight junctions through regulation of the MAPK-ERK pathway. Additionally, a novel role for Scribble in regulating tight junctions via the EMT inducer ZEB1/2 was identified. Finally, to investigate if Scribble loss cooperates with Ras signalling in vivo, I have taken a transgenic mouse model approach to assess how Scribble may be contributing to K-ras driven lung tumourigenesis. At both early and late stages of tumour progression, Scribble depletion promotes tumour growth and multiplicity leading to highly aggressive lesions. I further provide evidence suggesting that Scribble mediated deregulation of the downstream Ras effector pathways MAPK-ERK and JNK, drive the more malignant phenotype of Scribble depleted tumours. Through a combination of in vitro and in vivo approaches, the work in this thesis describes a multifunctional role for…

Subjects/Keywords: cancer; signalling; polarity; MAPK; Scribble

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Elsum, I. (2011). Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/36165

Chicago Manual of Style (16^th Edition):

Elsum, Imogen. “Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble.” 2011. Doctoral Dissertation, University of Melbourne. Accessed March 07, 2021. http://hdl.handle.net/11343/36165.

MLA Handbook (7^th Edition):

Elsum, Imogen. “Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble.” 2011. Web. 07 Mar 2021.

Vancouver:

Elsum I. Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble. [Internet] [Doctoral dissertation]. University of Melbourne; 2011. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/11343/36165.

Council of Science Editors:

Elsum I. Regulation of oncogenic Ras-MAPK signalling by the polarity protein Scribble. [Doctoral Dissertation]. University of Melbourne; 2011. Available from: http://hdl.handle.net/11343/36165

Georgia State University

10. 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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

King Abdullah University of Science and Technology

11. Alharbi, Siba I. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2020, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/664480

► Mitogen-activated protein kinases (MAPKs) are an important subfamily of protein kinases that are well conserved in all eukaryotes. MAPKs are the final component of a… (more)

▼ Mitogen-activated protein kinases (MAPKs) are an important subfamily of protein kinases that are well conserved in all eukaryotes. MAPKs are the final component of a three-tiered signaling module that regulates the activation of various essential cellular responses. They activate most of their substrates through catalyzing their phosphorylation. However, emerging evidence reveals that some MAPKs also possess non-catalytic functions. In particular, the human MAPK ERK2 can bind to DNA directly and mediate gene expression. The mechanism by which ERK2 binds to DNA is still unclear. In this work, we combined structural, biophysical and biochemical methods to confirm DNA binding by ERK2 and to investigate whether ERK2’s closest plant homolog MPK4 also binds to DNA. First, we identified a possible ERK2-like DNA consensus motif in plant MAPKs. We found that several plant MAPKs, including MPK4, harbor a basic motif (KARK/R or ARR/K) in a region corresponding to the ERK2 KAR motif reported to mediate DNA binding. Next, we determined the DNA binding affinity of ERK2 and MPK4 to different DNA fragments and found that MPK4 associated directly with DNA in vitro, albeit with a significantly lower affinity than did ERK2. Moreover, we observed that ERK2 and MPK4 showed preferred binding to different DNA sequences. Site-directed mutagenesis on the proposed DNA binding region of MPK4 greatly weakened DNA binding, confirming that MPK4 and ERK2 use the same structural elements to associate with DNA. Phosphorylation of the MAPKs through an upstream MKK affected the DNA binding capacity for both ERK2 and MPK4, although the effects differed. Lastly, we observed that a MPK4 mutant with a constitutively increased catalytic affinity displayed a markedly stronger DNA binding affinity compared to wild type MPK4 and phosphorylated MPK4. By demonstrating that the plant MPK4 associated with DNA in vitro, and that this association can be modified by phosphorylation and mutations, we open the possibility of additional kinase-independent functions in plant MAPKs. Advisors/Committee Members: Arold, Stefan T. (advisor), Hirt, Heribert (committee member), Al-Babili, Salim (committee member).

Subjects/Keywords: MAPK; MPK4; ERK2; DNA Binding

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Alharbi, S. I. (2020). A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/664480

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):

Alharbi, Siba I. “A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.” 2020. Thesis, King Abdullah University of Science and Technology. Accessed March 07, 2021. http://hdl.handle.net/10754/664480.

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

MLA Handbook (7^th Edition):

Alharbi, Siba I. “A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4.” 2020. Web. 07 Mar 2021.

Vancouver:

Alharbi SI. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2020. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10754/664480.

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

Council of Science Editors:

Alharbi SI. A Comparative DNA Binding Study of the Human MAPK ERK2 and the Plant MAPK MPK4. [Thesis]. King Abdullah University of Science and Technology; 2020. Available from: http://hdl.handle.net/10754/664480

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

12. 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, Université Paris-Saclay (ComUE)

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

►

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)

▼

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

Record Details Similar Records Cite « Share

❌

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). Université Paris-Saclay (ComUE). 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, Université Paris-Saclay (ComUE). Accessed March 07, 2021. 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. 07 Mar 2021.

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]. Université Paris-Saclay (ComUE); 2015. [cited 2021 Mar 07]. 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]. Université Paris-Saclay (ComUE); 2015. Available from: http://www.theses.fr/2015SACLS151

13. 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

►

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)

▼

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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

14. 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

►

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)

▼

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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

15. 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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

NSYSU

16. 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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Hsu C. The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells. [Internet] [Thesis]. NSYSU; 2004. [cited 2021 Mar 07]. 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 Newcastle

17. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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 Adelaide

18. Merrett, James Edward. Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs).

Degree: 2020, University of Adelaide

URL: http://hdl.handle.net/2440/126953

► The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are a family of serine/threonine protein kinases that are activated downstream of the ERK1/2 (extracellular regulated kinase) and… (more)

▼ The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are a family of serine/threonine protein kinases that are activated downstream of the ERK1/2 (extracellular regulated kinase) and p38α/β MAPK pathways. The MNKs are encoded on separate genes, Mknk1 and Mknk2, giving rise to two proteins in mice, MNK1 and MNK2, respectively. The MNKs have previously been implicated in metabolic disease and shown to regulate weight gain in mice in response to an energy-rich high-fat diet (HFD). In particular, MNK2-knockout (KO) mice are protected from HFD-induced weight gain and therefore, MNK2 is proposed to regulate adipose tissue expansion. Adipose tissue acts as a stable, long term energy reserve that can be readily mobilised, and plays an important role in regulating whole-body energy homeostasis. It is suggested that MNK activity may be required for the differentiation of new fat cells (adipocytes) and increasing adipocyte lipid storage; however, the function and underlying mechanisms of the MNKs in these processes are yet to be determined. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, the role of the MNKs in adipocyte differentiation (adipogenesis) and lipid storage was investigated. Inhibition of MNK activity using specific inhibitors failed to impair adipogenesis or lipid accumulation, suggesting MNK activity is not required for adipocyte differentiation and does not regulate lipid storage. Despite this, expression analysis revealed MNK2 to be the predominant isoform in adipose depots. Therefore, to investigate the role of MNK2 specifically in these processes, a 3T3-L1-2KO cell model was generated using CRISPR-Cas9 and small-interfering RNA (siRNA)-mediated knockdown of Mknk2 was also used. Intriguingly, the knockdown of MNK2 was found to decrease lipid accumulation in adipocytes, suggesting non-catalytic functions of MNK2 regulate adipocyte metabolism. It was revealed that MNK2 likely regulates the levels of two major lipogenic transcription factors, ChREBP (carbohydrate response element binding protein) and LPIN1 (Lipin-1), through novel protein-protein interactions. These factors are largely responsible for activating expression of genes in synthetic processes that promote lipid storage in adipocytes, namely de novo lipogenesis (DNL) and triglyceride synthesis. The knockdown of MNK2 also increases the expression of HSL (hormone-sensitive lipase) which increases the breakdown (lipolysis) of stored triglyceride. Herein, a model in which the knockdown of MNK2 in vitro accounts for a significant reduction in adipocyte lipid accumulation is proposed. These findings identify MNK2 as a regulator of adipocyte metabolism and reveal some of the underlying MNK2-driven mechanisms that promote adipose tissue expansion. The development of an MNK2-targeted therapy may therefore be a useful intervention for reducing weight caused by excessive nutrient intake. Advisors/Committee Members: Proud, Christopher (advisor), Psaltis, Peter (advisor), School of Biological Sciences (school).

Subjects/Keywords: adipocyte; adipogenesis; adipocyte differentiation; metabolism; MAPK; MNK

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Merrett, J. E. (2020). Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs). (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/126953

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):

Merrett, James Edward. “Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs).” 2020. Thesis, University of Adelaide. Accessed March 07, 2021. http://hdl.handle.net/2440/126953.

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

MLA Handbook (7^th Edition):

Merrett, James Edward. “Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs).” 2020. Web. 07 Mar 2021.

Vancouver:

Merrett JE. Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs). [Internet] [Thesis]. University of Adelaide; 2020. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2440/126953.

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

Council of Science Editors:

Merrett JE. Control of adipocyte differentiation and metabolism by mitogen-activated protein kinase (MAPK)- interacting kinases (MNKs). [Thesis]. University of Adelaide; 2020. Available from: http://hdl.handle.net/2440/126953

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

Colorado State University

19. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

University of Manchester

20. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Gaffey K. Glucocorticoid resistance in COPD : the role of p38 MAPK. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Mar 07]. 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

George Mason University

21. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Voss K. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . [Internet] [Thesis]. George Mason University; 2014. [cited 2021 Mar 07]. 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

University of South Florida

22. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Wu J. Regulation of Extracellular Signal-Regulated Kinase by Histone Deacetylase 6. [Internet] [Thesis]. University of South Florida; 2017. [cited 2021 Mar 07]. 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

Duquesne University

23. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

Université de Sherbrooke

24. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Couture J. Rôle de la MAPKKK DLK dans l'adipogenèse. [Internet] [Doctoral dissertation]. Université de Sherbrooke; 2011. [cited 2021 Mar 07]. 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

University of Louisville

25. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Aulakh KB. Specific b alleles matter in phytopathogenic Ustilago maydis. [Internet] [Masters thesis]. University of Louisville; 2012. [cited 2021 Mar 07]. 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

26. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Maddison LE. Experimental and Theoretical Modelling of the MAPK Pathway. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Mar 07]. 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

University of New South Wales

27. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

Wright State University

28. 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

Record Details Similar Records Cite « Share

❌

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

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 March 07, 2021. 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. 07 Mar 2021.

Vancouver:

Vallabhaneni S. Investigating the Function of ERK3 In Lung Tumor Progression. [Internet] [Masters thesis]. Wright State University; 2018. [cited 2021 Mar 07]. 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

King Abdullah University of Science and Technology

29. Alhoraibi, Hanna. Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2019, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/644897

► Plants are sessile organisms and constantly encounter a myriad of pathogens; therefore, they rely on highly effective defense system for their survival. Our understanding of… (more)

▼ Plants are sessile organisms and constantly encounter a myriad of pathogens; therefore, they rely on highly effective defense system for their survival. Our understanding of how plant immunity is triggered and regulated has seen tremendous progress over the last two decades, with many important players identified in the model systems, Arabidopsis thaliana. Mitogen activated protein kinases play a central role in signal transduction in biotic and abiotic stresses. MAPK pathways are regulated by three-interlinked protein kinases (MAPKKK, MAPKK, MAPK), which are sequentially activated by phosphorylation. The activation of the three MAPKs MPK3, MPK4 and MPK6 is one of the earliest cellular responses following pathogen attack leading to the phosphorylation of appropriate cytosolic or nuclear targets to regulate cellular processes. However, only few targets of MPK3, MPK4 and MPK6 have been identified and validated so far and many MAPK substrates remain to be discovered. We performed largescale phosphoproteomics on mock treated and flg22 treated WT and the three loss-of-function mutants mpk3, mpk4 and mpk6 to identify novel MAPKs substrates and their cellular functions in response to pathogen attack. We identify and validated some of the differentially phosphorylated cytosolic and chromatin targets of MPK3, MPK4 and MPK6. DEK2, a nuclear protein involved in multiple chromatin-related processes, was identified in the phosphoproteomics screen as an in vivo target of MPK6 and it interacts in planta and is phosphorylated in vitro by the three immune MAPKs. dek2 loss-of-function mutants were susceptible to bacterial as well as fungal pathogens. Additionally, transcriptome data of the dek2-1 mutant show that DEK2 is a transcriptional repressor inclusive of defense related genes and hormone synthesis and signaling genes. We determined that DEK2 is a reader of the histone mark, H3K9me1, by Microscale thermophoresis. From ChIP-Seq analysis, DEK2 was found to be enriched at class I TCP binding motif regions. We further need to determine whether DEK2 binds to TCP transcription factors directly or indirectly. Finally, based on our data we postulate a hypothetical working model for the function of DEK2 as a transcriptional repressor and a reader of H3K9me1 mark. Advisors/Committee Members: Hirt, Heribert (advisor), Rayapuram, Naganand (committee member), Colcombet, Jean (committee member), Blilou, Ikram (committee member), Arold, Stefan T. (committee member).

Subjects/Keywords: Arabidopsis; Immunity; Phosphoproteomics; Epigenetics; MAPK Signaling; AtDEK2

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Alhoraibi, H. (2019). Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/644897

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):

Alhoraibi, Hanna. “Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana.” 2019. Thesis, King Abdullah University of Science and Technology. Accessed March 07, 2021. http://hdl.handle.net/10754/644897.

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

MLA Handbook (7^th Edition):

Alhoraibi, Hanna. “Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana.” 2019. Web. 07 Mar 2021.

Vancouver:

Alhoraibi H. Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2019. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10754/644897.

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

Council of Science Editors:

Alhoraibi H. Identification, validation and characterization of putative cytosolic and nuclear targets of immune MAPKs involved in biotic stress responses in Arabidopsis thaliana. [Thesis]. King Abdullah University of Science and Technology; 2019. Available from: http://hdl.handle.net/10754/644897

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. 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

►

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)

▼

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

Record Details Similar Records Cite « Share

❌

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 March 07, 2021. 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. 07 Mar 2021.

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 2021 Mar 07]. 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

Open Access Theses and Dissertations