You searched for subject:(Hippo).
Showing records 1 – 30 of
217 total matches.
◁ [1] [2] [3] [4] [5] [6] [7] [8] ▶
University of Edinburgh
1.
Rausch, Valentina Jana Laura.
Hippo pathway regulates caveolae expression and mediates flow response via caveolae.
Degree: PhD, 2020, University of Edinburgh
URL: http://hdl.handle.net/1842/36706 
► The Hippo pathway is a key regulator of cell survival, proliferation and tissue homeostasis. In addition, it is vital for development and regeneration. The activity…
(more)
▼ The Hippo pathway is a key regulator of cell survival, proliferation and tissue homeostasis. In addition, it is vital for development and regeneration. The activity of the Hippo pathway depends on intra- and extra-cellular signals and is tightly regulated by diffusible chemicals as well as mechanical stimuli. The pathway comprises of a kinase cascade that controls the activity of YAP and TAZ, homologous transcriptional co-activators. Despite its central role in most cells the overall regulation of the Hippo pathway, especially originating from the plasma membrane, is not yet fully understood. Caveolae are 50-100 nm bulb-shaped plasma membrane invaginations that function in endocytosis, protection from mechanical stress and in cell signalling. Hence, the aim was to identify if caveolae and the Hippo pathway are functionally linked. This thesis reveals that the central caveolar components CAVEOLIN1 and CAVIN1 depend on YAP/TAZ. CAVEOLIN1 and CAVIN1 are direct YAP-TEAD target genes and YAP/TAZ are essential for the expression of caveolar components in mammalian cells and in zebrafish. Moreover, CAVEOLIN1 dictates YAP/TAZ subcellular localisation and inhibits their activity. Notably, in cells with diminished levels of caveolae, YAP/TAZ are hyperactive (nuclear), which led to increased induction of gene transcription. Finally, the activation of YAP/TAZ by shear stress is partly dependent on caveolae. These data link caveolae to Hippo pathway signalling in the context of cellular responses to mechanical stimuli and suggest feedback regulation between the Hippo pathway co-transcriptional activators YAP/TAZ and essential caveolae components.
Subjects/Keywords: Hippo pathway; Caveolae
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rausch, V. J. L. (2020). Hippo pathway regulates caveolae expression and mediates flow response via caveolae. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/36706
Chicago Manual of Style (16th Edition):
Rausch, Valentina Jana Laura. “Hippo pathway regulates caveolae expression and mediates flow response via caveolae.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed January 19, 2021.
http://hdl.handle.net/1842/36706.
MLA Handbook (7th Edition):
Rausch, Valentina Jana Laura. “Hippo pathway regulates caveolae expression and mediates flow response via caveolae.” 2020. Web. 19 Jan 2021.
Vancouver:
Rausch VJL. Hippo pathway regulates caveolae expression and mediates flow response via caveolae. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/1842/36706.
Council of Science Editors:
Rausch VJL. Hippo pathway regulates caveolae expression and mediates flow response via caveolae. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: http://hdl.handle.net/1842/36706
University of Edinburgh
2.
Rausch, Valentina Jana Laura.
Hippo pathway regulates caveolae expression and mediates flow response via caveolae.
Degree: PhD, 2020, University of Edinburgh
URL: https://doi.org/10.7488/era/13
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799030
► The Hippo pathway is a key regulator of cell survival, proliferation and tissue homeostasis. In addition, it is vital for development and regeneration. The activity…
(more)
▼ The Hippo pathway is a key regulator of cell survival, proliferation and tissue homeostasis. In addition, it is vital for development and regeneration. The activity of the Hippo pathway depends on intra- and extra-cellular signals and is tightly regulated by diffusible chemicals as well as mechanical stimuli. The pathway comprises of a kinase cascade that controls the activity of YAP and TAZ, homologous transcriptional co-activators. Despite its central role in most cells the overall regulation of the Hippo pathway, especially originating from the plasma membrane, is not yet fully understood. Caveolae are 50-100 nm bulb-shaped plasma membrane invaginations that function in endocytosis, protection from mechanical stress and in cell signalling. Hence, the aim was to identify if caveolae and the Hippo pathway are functionally linked. This thesis reveals that the central caveolar components CAVEOLIN1 and CAVIN1 depend on YAP/TAZ. CAVEOLIN1 and CAVIN1 are direct YAP-TEAD target genes and YAP/TAZ are essential for the expression of caveolar components in mammalian cells and in zebrafish. Moreover, CAVEOLIN1 dictates YAP/TAZ subcellular localisation and inhibits their activity. Notably, in cells with diminished levels of caveolae, YAP/TAZ are hyperactive (nuclear), which led to increased induction of gene transcription. Finally, the activation of YAP/TAZ by shear stress is partly dependent on caveolae. These data link caveolae to Hippo pathway signalling in the context of cellular responses to mechanical stimuli and suggest feedback regulation between the Hippo pathway co-transcriptional activators YAP/TAZ and essential caveolae components.
Subjects/Keywords: Hippo pathway; Caveolae
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rausch, V. J. L. (2020). Hippo pathway regulates caveolae expression and mediates flow response via caveolae. (Doctoral Dissertation). University of Edinburgh. Retrieved from https://doi.org/10.7488/era/13 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799030
Chicago Manual of Style (16th Edition):
Rausch, Valentina Jana Laura. “Hippo pathway regulates caveolae expression and mediates flow response via caveolae.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed January 19, 2021.
https://doi.org/10.7488/era/13 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799030.
MLA Handbook (7th Edition):
Rausch, Valentina Jana Laura. “Hippo pathway regulates caveolae expression and mediates flow response via caveolae.” 2020. Web. 19 Jan 2021.
Vancouver:
Rausch VJL. Hippo pathway regulates caveolae expression and mediates flow response via caveolae. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Jan 19].
Available from: https://doi.org/10.7488/era/13 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799030.
Council of Science Editors:
Rausch VJL. Hippo pathway regulates caveolae expression and mediates flow response via caveolae. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: https://doi.org/10.7488/era/13 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799030
University of St. Andrews
3.
Angus, Liselotte.
Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
.
Degree: 2011, University of St. Andrews
URL: http://hdl.handle.net/10023/2489;
http://dx.doi.org/10.1117/1.3430730
► The Salvador/Warts/Hippo (Hippo) pathway defines a novel signalling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals.…
(more)
▼ The Salvador/Warts/
Hippo (
Hippo) pathway defines a novel signalling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The
Hippo pathway was initially utilised in D. melanogaster, where the Expanded protein acts in the
Hippo signalling cascade to control organ size. Willin is the proposed
human orthologue of Expanded and the aim of this thesis is to investigate
whether willin can activate the mammalian
Hippo signalling pathway. Ectopic willin expression causes an increase in phosphorylation of the core
Hippo signalling pathway components MST1/2, LATS1 and YAP, an effect which can be antagonised by ezrin. In MCF10A cells, willin over-expression
antagonises a YAP-induced epithelial-to-mesenchymal transition via the N-
terminal FERM (Four-point-one Ezrin Radixin Moesin) domain of willin. Preliminary results show that willin is expressed within the sciatic nerve of rat and mice, and within the neuromast cells in the zebrafish; suggesting that willin and the
Hippo pathway may play a vital role in the developmental regulation within the peripheral nervous system. To conclude, willin influences
Hippo signalling activity by activating the core
Hippo pathway kinase cassette
in mammalian cells.
Advisors/Committee Members: Gunn-Moore, Frank J (advisor).
Subjects/Keywords: Willin;
Hippo pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Angus, L. (2011). Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
. (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/2489; http://dx.doi.org/10.1117/1.3430730
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Angus, Liselotte. “Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
.” 2011. Thesis, University of St. Andrews. Accessed January 19, 2021.
http://hdl.handle.net/10023/2489; http://dx.doi.org/10.1117/1.3430730.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Angus, Liselotte. “Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
.” 2011. Web. 19 Jan 2021.
Vancouver:
Angus L. Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
. [Internet] [Thesis]. University of St. Andrews; 2011. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/10023/2489; http://dx.doi.org/10.1117/1.3430730.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Angus L. Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
. [Thesis]. University of St. Andrews; 2011. Available from: http://hdl.handle.net/10023/2489; http://dx.doi.org/10.1117/1.3430730
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
4.
Yuan, Fang.
Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry.
Degree: 2013, University of Toronto
URL: http://hdl.handle.net/1807/43372
► The Hippo signaling pathway offers an intrinsic mechanism to control organ sizes, and dysfunction of this pathway can often lead to cancer. Great advancement has…
(more)
▼ The Hippo signaling pathway offers an intrinsic mechanism to control organ sizes, and dysfunction of this pathway can often lead to cancer. Great advancement has been made in recent years into understanding this pathway. Despite all this invaluable knowledge, much remains to be explored. Mass spectrometry offers an unbiased approach to characterize the interactome of any protein of interest and is particularly powerful for identifying potential novel regulators of signalling pathways. I therefore set out to characterize the interactome of all the Hippo pathway main components using mass spectrometry, with the goal of uncovering novel regulatory mechanism(s) of the Hippo pathway. In the end, I was able to identify over 250 novel interactors of the Hippo pathway in total. This study demonstrates the utility of mass spectrometry to identify novel regulators of the Hippo pathway and characterization of one such interactor.
MAST
Advisors/Committee Members: Wrana, Jeffrey, Molecular and Medical Genetics.
Subjects/Keywords: hippo pathway; mass spectrometry; 0307
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yuan, F. (2013). Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/43372
Chicago Manual of Style (16th Edition):
Yuan, Fang. “Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry.” 2013. Masters Thesis, University of Toronto. Accessed January 19, 2021.
http://hdl.handle.net/1807/43372.
MLA Handbook (7th Edition):
Yuan, Fang. “Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry.” 2013. Web. 19 Jan 2021.
Vancouver:
Yuan F. Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry. [Internet] [Masters thesis]. University of Toronto; 2013. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/1807/43372.
Council of Science Editors:
Yuan F. Characterization of the Interactome of the Hippo Tumour Suppressor Pathway using Mass Spectrometry. [Masters Thesis]. University of Toronto; 2013. Available from: http://hdl.handle.net/1807/43372
5.
金, 善龍.
Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン.
Degree: 博士(バイオサイエンス), 2017, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学
URL: http://hdl.handle.net/10061/11536
Subjects/Keywords: Hippo pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
金, . (2017). Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/11536
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
金, 善龍. “Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン.” 2017. Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed January 19, 2021.
http://hdl.handle.net/10061/11536.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
金, 善龍. “Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン.” 2017. Web. 19 Jan 2021.
Vancouver:
金 . Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; 2017. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/10061/11536.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
金 . Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway : Hippoシグナル伝達経路におけるMOB1の自己阻害と解除の構造基盤; Hippo シグナル デンタツ ケイロ ニ オケル MOB1 ノ ジコ ソガイ ト カイジョ ノ コウゾウ キバン. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; 2017. Available from: http://hdl.handle.net/10061/11536
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Queen Mary, University of London
6.
Fulford, Alexander.
Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling.
Degree: PhD, 2018, Queen Mary, University of London
URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/31794
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766092
► The Hippo Pathway is a highly conserved regulator of tissue growth and size determination, limiting the activity of the transcriptional co-activator Yorkie (Yki), which promotes…
(more)
▼ The Hippo Pathway is a highly conserved regulator of tissue growth and size determination, limiting the activity of the transcriptional co-activator Yorkie (Yki), which promotes proliferation and inhibits apoptosis. Hippo signalling integrates and transduces cell polarity and cell-cell adhesion inputs thereby responding to the state of tissue architecture. The transmembrane apical polarity protein Crumbs (Crb) controls the activity of Yki by regulating Expanded (Ex), a protein that promotes Hippo signalling through kinase-dependent and -independent mechanisms to robustly inhibit Yki activity. Crb plays a dual role in the regulation of Ex by controlling its apical localisation, facilitating Yki inhibition, and by promoting Ex degradation, thus activating Yki. Crb regulates the stability of Ex by stimulating a phosphorylation-dependent ubiquitylation and proteasomal degradation. Characterisation of the precise mechanisms by which Crb regulates Ex has been the focus of this thesis. Based on candidates identified by mass spectrometry and from literature, the Casein Kinase 1 (CK1) family of kinases, and the deubiquitylating enzyme (DUB) Usp2 have both been identified as novel regulators of Ex stability. CK1s promote Ex phosphorylation and degradation, acting as Ex inhibitors, while Usp2 promotes Ex function by promoting its stabilisation. Furthermore, in a screen to identify DUBs that regulate Drosophila adult wing size, CG10889 has been established as a novel regulator of growth that interacts with members of the Hippo pathway.
Subjects/Keywords: Tumour Biology; Hippo Pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fulford, A. (2018). Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/31794 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766092
Chicago Manual of Style (16th Edition):
Fulford, Alexander. “Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling.” 2018. Doctoral Dissertation, Queen Mary, University of London. Accessed January 19, 2021.
http://qmro.qmul.ac.uk/xmlui/handle/123456789/31794 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766092.
MLA Handbook (7th Edition):
Fulford, Alexander. “Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling.” 2018. Web. 19 Jan 2021.
Vancouver:
Fulford A. Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2018. [cited 2021 Jan 19].
Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/31794 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766092.
Council of Science Editors:
Fulford A. Investigating the role of phosphorylation and ubiquitylation dependent regulation of Hippo signalling. [Doctoral Dissertation]. Queen Mary, University of London; 2018. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/31794 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766092
7.
Boone, Émilie.
Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth.
Degree: Docteur es, Interactions moléculaires et cellulaires, 2016, Nice
URL: http://www.theses.fr/2016NICE4026
► Au cours du développement, les organismes croissent de façon harmonieuse suivant un programme génétique intrinsèque et en adaptation avec les conditions environnementales. Chaque tissu atteint…
(more)
▼ Au cours du développement, les organismes croissent de façon harmonieuse suivant un programme génétique intrinsèque et en adaptation avec les conditions environnementales. Chaque tissu atteint une taille cible qui est proportionnelle à la taille finale des autres organes et à celle de l’organisme. Des expériences de régénération effectuées sur différents modèles animaux ont révélé que chaque organe possède un programme autonome de croissance. Ainsi, des mécanismes de coordination entre la croissance tissulaire et le programme de développement sont nécessaires afin d’assurer une régulation fine de l’allométrie avant le passage du stade juvénile au stade adulte fixant la taille finale du corps. Dilp8 (Drosophila Insulin Like Peptide 8) est une hormone analogue aux peptides de la famille des insulines/relaxines. Elle est produite par les tissus dont la croissance est lésée, en régénération ou néoplasique. dilp8 inhibe la production d’hormone stéroïde et retarde ainsi le passage à la forme adulte. Les mutants dilp8 présentent une augmentation du bruit développemental qui se traduit par une perte de la symétrie bilatérale des organes (asymétrie fluctuante FA). Ceci suggère un rôle de dilp8 dans la coordination de la croissance entre les organes. Au cours de ma thèse, j’ai pu montrer que la voie de signalisation Hippo, son activateur transcriptionnel Yorkie et son co-partenaire Scalloped régulent directement les niveaux transcriptionnels de dilp8 via un Hippo Responsive Element (HRE) présent dans le promoteur de dilp8. La voie Hippo joue un rôle clé dans le contrôle de la taille des organes en couplant les paramètres biomécaniques des tissus avec la prolifération cellulaire.
Growth of different body parts needs to be coordinated and scaled with the overall body size to give rise to adults of correct proportions. Since different organs follow autonomous growth programs, mechanisms must operate to ensure that each organ has reached an appropriate size before proceeding through developmental transitions. We recently identified Dilp8 (Drosophila insulin-like peptide 8) as a key hormone in coupling organ growth with animal maturation. Dilp8 is secreted from abnormally growing tissues and acts on the brain complex to delay pupariation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in coordinating organ growth and ensuring developmental stability. Identifying signals that control dilp8 expression is therefore likely to provide a better understanding of organ size assessment mechanisms. The Hippo tumour suppressor pathway plays a major function in restricting organ growth by promoting cell cycle exit and apoptosis. Hippo signalling is responsive to the mechanical forces operating in growing organs making it an ideal candidate for assessing organ size. Activation of the Hippo pathway restricts nuclear translocation of the transcriptional co-activator Yorkie (Yki), which together with its DNA-binding partner Scalloped (Sd), regulates downstream growth-promoting…
Advisors/Committee Members: Leopold, Pierre (thesis director), Colombani, Julien (thesis director).
Subjects/Keywords: Cancer; Croissance; Hippo; Hormones; Dilp8; Cancer; Growth; Hippo; Hormones; Dilp8
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Boone, E. (2016). Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth. (Doctoral Dissertation). Nice. Retrieved from http://www.theses.fr/2016NICE4026
Chicago Manual of Style (16th Edition):
Boone, Émilie. “Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth.” 2016. Doctoral Dissertation, Nice. Accessed January 19, 2021.
http://www.theses.fr/2016NICE4026.
MLA Handbook (7th Edition):
Boone, Émilie. “Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth.” 2016. Web. 19 Jan 2021.
Vancouver:
Boone E. Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth. [Internet] [Doctoral dissertation]. Nice; 2016. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2016NICE4026.
Council of Science Editors:
Boone E. Étude de dilp8, une hormone de couplage de la croissance tissulaire : The study of dilp8, a new hormone coordinating organ growth. [Doctoral Dissertation]. Nice; 2016. Available from: http://www.theses.fr/2016NICE4026
8.
Ben Mimoun, Saber.
L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein.
Degree: Docteur es, Médecine. Oncogénèse, 2018, Sorbonne Paris Cité
URL: http://www.theses.fr/2018USPCC231
► Les contacts cellule-cellule activent des signaux contrôlant le processus d'inhibition de contact, un phénomène par lequel les cellules normales cultivées en monocouches présentent une prolifération…
(more)
▼ Les contacts cellule-cellule activent des signaux contrôlant le processus d'inhibition de contact, un phénomène par lequel les cellules normales cultivées en monocouches présentent une prolifération réduite, voire un arrêt de croissance, lorsqu'elles atteignent la confluence. Ceci est en partie dû à l'activation de la voie Hippo qui entraîne la phosphorylation et l'exclusion nucléaire des co-activateurs transcriptionnels YAP et TAZ. Ceprocessus physiologique est crucial pour le maintien de l'homéostasie tissulaire et estsouvent perdu au cours de la progression néoplasique ou de la transformation in vitro.Le facteur de croissance transformant ß (TGF-ß) est une cytokine qui joue aussi un rôle pléiotropique dans l'homéostasie et la carcinogenèse. Contrairement à la voie de l'Hippo, savoie canonique est initiée par l'activation des récepteurs membranaires, qui phosphorylent ensuite les facteurs de transcription cytoplasmiques SMADs, conduisant à leur translocation nucléaire et à l'induction des gènes cibles du TGF-ß. La densité cellulaire et la signalisation d'Hippo ont été rapportées comme bloquant les réponses du TGF-ß, par la capacité du phospho-YAP/TAZ à séquestrer les complexes SMAD activés par le TGF-ß dans le cytoplasme.Ainsi, le but de mon projet était d'étudier l'interaction entre la voie Hippo et la voie TGF-ß dans le contexte de la densité cellulaire.Dans la première partie de ce travail, nous avons démontré que, bien que l'activation de la voie Hippo par la densité cellulaire se produise dans les cellules épithéliales et non épithéliales, le blocage de la voie TGF-ß se produit uniquement dans les cellules épithéliales polarisées. En outre, nous avons fourni des preuves que la polarisation des cellules épithéliales interfère avec la signalisation du TGF-ß bien en amont et indépendamment de la localisation de YAP/TAZ. Nos résultats ont conduit à l'établissement d'un nouveau modèle,spécifique aux cellules épithéliales polarisées, où le scellement de la perméabilité paracellulaire empêche le ligand de TGF-ß sécrété apicalement d'accéder à ses récepteurs qui sont retenus au domaine basolatéral de la membrane cytoplasmique.Dans la seconde partie de ce manuscrit, basée sur la caractérisation des paramètres biophysiques liés à la fonction barrière de l'épithélium, nous avons démontré que la mesure de la perméabilité trans-épithéliale (TER) pouvait être utilisée comme outil de suivi et de vérification de la polarité des épithéliums étanches. Considérant l'implication des jonctions serrées (JSs) dans la polarité épithéliale, nous avons examiné le rôle de l'une de ses protéines cytoplasmiques, ZO-1. Nos résultats ont montré que ZO-1 n'est pas nécessaire pour les fonctions de barrière et de clôture des JSs dans les cellules EpH4 polarisées. Ainsi,nous concluons que ZO-1 n'est pas un bon marqueur de la polarité des cellules épithéliales et n'est pas essentiel pour leur résistance au TGF-ß apical.
Cell-cell contacts drive signals controlling the process of contact inhibition, a phenomen on whereby normal cells grown in…
Advisors/Committee Members: Mauviel, Alain (thesis director).
Subjects/Keywords: Hippo; Polarité apico-basale; Hippo; Apico-basal polarity
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ben Mimoun, S. (2018). L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCC231
Chicago Manual of Style (16th Edition):
Ben Mimoun, Saber. “L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021.
http://www.theses.fr/2018USPCC231.
MLA Handbook (7th Edition):
Ben Mimoun, Saber. “L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein.” 2018. Web. 19 Jan 2021.
Vancouver:
Ben Mimoun S. L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2018USPCC231.
Council of Science Editors:
Ben Mimoun S. L'interaction entre les voies de signalisation TGF-B et Hippo : implication de la polarité apico-basale et de le protéine ZO-1 : The crosstalk between TGF-ß and Hippo signaling pathways : implication of apico-basal polarity and ZO-1 protein. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCC231
9.
Srivastava, Diwas.
Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif.
Degree: Docteur es, Biologie Santé, 2019, Montpellier
URL: http://www.theses.fr/2019MONTT015
► La voie Hippo est une voie conservée impliquée dans la croissance des tissus et la suppression de tumeurs. Des études ont démontré son implication dans…
(more)
▼ La voie Hippo est une voie conservée impliquée dans la croissance des tissus et la suppression de tumeurs. Des études ont démontré son implication dans le développement des cancers chez l'homme. Cette cascade contrôle l'activité du co-activateur transcriptionnel Yorkie (Yki) chez la drosophile et de la protéine YAP (Yes Associated Protein) chez les mammifères. En raison de l'épissage alternatif de leur transcrits, les protéines Yki et YAP existent sous deux isoformes contenant un domaine WW (Yki1/YAP1) ou deux (Yki2/YAP2). Puisque les domaines WW sont essentiels pour l’interaction avec des partenaires spécifiques, l’inclusion alternative de ce domaine dans la protéine Yki/YAP peut remodeler leur réseau d’interaction et donc leur activité. La régulation et les conséquences fonctionnelles de l’épissage alternatif de yki / YAP in vivo sont inconnues.Dans le cadre de ce doctorat, nous avons constaté que la déplétion du facteur d’épissage B52 chez la drosophile réduit l’inclusion de l’exon alternatif dans l’ARNm de yki et favorise l’expression de l’isoforme Yki1 aux dépens de l’isoforme Yki2. La déplétion en B52 dans l'aile réduit la croissance et l'activité de Yki. Nous montrons que l'isoforme Yki1 est une version atténuée de la protéine Yki qui peut entrer en concurrence avec l'isoforme Yki2 dans le noyau. Pour déterminer le rôle de l’épissage alternatif de yki in vivo et l'importance de l'isoforme courte Yki1, nous avons abrogé cet épissage en utilisant la technologie CRISPR/Cas9 et avons créé des mouches capables d'exprimer uniquement l'isoforme Yki2. Ces mouches yki2only sont viables mais présentent un phénotype aléatoire d’ailes asymétriques. Cette augmentation de l'«asymétrie fluctuante», qui traduit une déviation par rapport au développement normal, suggère que l’épissage alternatif de yki est crucial pour la stabilité développementale. Ces résultats mettent en évidence un nouveau niveau de modulation de la voie Hippo via l’épissage alternatif de yki.L'inclusion alternative du deuxième domaine WW est une caractéristique conservée entre Yki et YAP. Cela conforte l'idée que les isoformes Yki1 et YAP1 ont une fonction importante in vivo et que l'épissage alternatif de yki/YAP est un mécanisme conservé de contrôle de la voie Hippo. Cette étude ouvre de nouvelles perspectives pour la modulation de la voie Hippo dans les cellules cancéreuses en modifiant l’épissage alternatif de YAP.
The Hippo pathway is a conserved pathway involved in tissue growth and tumor suppression. Studies have demonstrated its significance in the development of human cancers. This cascade controls the activity of the transcription co-activator Yorkie (Yki) in flies and Yes-associated protein (YAP) in mammals. Due to Alternative Splicing (AS), both Yki and YAP proteins exist as two isoforms containing one (Yki1/YAP1) or two (Yki2/YAP2) WW domains. Since WW domains are essential for interaction with specific partners, the alternative inclusion of this domain in Yki/YAP protein may remodel their interaction network and therefore their activity.…
Advisors/Committee Members: Juge, François (thesis director), Tazi, Jamal (thesis director).
Subjects/Keywords: Drosophile; Voie Hippo; Épissage alternatif; Drosophila; Hippo pathway; Alternative splicing
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Srivastava, D. (2019). Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2019MONTT015
Chicago Manual of Style (16th Edition):
Srivastava, Diwas. “Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif.” 2019. Doctoral Dissertation, Montpellier. Accessed January 19, 2021.
http://www.theses.fr/2019MONTT015.
MLA Handbook (7th Edition):
Srivastava, Diwas. “Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif.” 2019. Web. 19 Jan 2021.
Vancouver:
Srivastava D. Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif. [Internet] [Doctoral dissertation]. Montpellier; 2019. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2019MONTT015.
Council of Science Editors:
Srivastava D. Modulation of hippo pathway by alternative splicing : Modulation de la voie Hippo par épissage alternatif. [Doctoral Dissertation]. Montpellier; 2019. Available from: http://www.theses.fr/2019MONTT015
University of California – San Diego
10.
Plouffe, Steven W.
Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ.
Degree: Biomedical Sciences, 2018, University of California – San Diego
URL: http://www.escholarship.org/uc/item/15k9q60f
► The Hippo pathway and its downstream effectors, transcriptional coactivators YAP and TAZ, are important for regulating tissue homeostasis and their dysregulation has been implicated in…
(more)
▼ The Hippo pathway and its downstream effectors, transcriptional coactivators YAP and TAZ, are important for regulating tissue homeostasis and their dysregulation has been implicated in many human diseases and cancer. However, it is not clear how the Hippo pathway becomes dysregulated because few mutations have been identified in Hippo pathway components. Therefore, recent work in the Hippo field has focused on identifying upstream regulators of the Hippo pathway. Nevertheless, it is not always clear which components are most physiologically relevant in regulating YAP/TAZ. To provide an overview of which components are most physiologically relevant in regulating YAP/TAZ, we used CRISPR/Cas9 to create knockout cell lines for many of these components and tested their responses to a variety of physiological signals to determine which components are most critical in regulating YAP/TAZ. By this approach, we demonstrate that NF2 and RHOA are important regulators of YAP/TAZ, and TAOK1/3 are direct kinases for LATS1/2.Additionally, YAP and TAZ are traditionally viewed as being largely redundant, although there are evolutionary, structural, and physiological differences that suggest there may be differences in how they are regulated and in their downstream functions. To delineate any differences between YAP and TAZ, we compared LATS1/2 KO cells, in which YAP/TAZ are constitutively-active, YAP KO, TAZ KO, and YAP/TAZ KO cells, in which YAP/TAZ are constitutively-inactive. We found that inactivation of YAP had a much greater negative effect on many measures of cell physiology, including cell spreading, cell volume, glucose uptake and metabolism, cell proliferation, and migration, while YAP activation in the LATS1/2 KO cells had the opposite effect. Differences between YAP and TAZ may be explained by differences in protein stability and expression, as YAP protein expression is much higher than that of TAZ. We also identified some differences in the transcriptional profiles induced by YAP and TAZ, suggesting that, although they are largely similar, there may be important distinctions between YAP and TAZ.
Subjects/Keywords: Pharmacology; CRISPR/Cas9; Hippo pathway; TAZ; YAP
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Plouffe, S. W. (2018). Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/15k9q60f
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Plouffe, Steven W. “Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ.” 2018. Thesis, University of California – San Diego. Accessed January 19, 2021.
http://www.escholarship.org/uc/item/15k9q60f.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Plouffe, Steven W. “Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ.” 2018. Web. 19 Jan 2021.
Vancouver:
Plouffe SW. Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 19].
Available from: http://www.escholarship.org/uc/item/15k9q60f.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Plouffe SW. Characterization of Hippo pathway regulation and the physiological implications of its downstream effectors YAP and TAZ. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/15k9q60f
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Queens University
11.
Alharbi, Adel.
Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
.
Degree: Pathology and Molecular Medicine, 2014, Queens University
URL: http://hdl.handle.net/1974/12464
► The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in…
(more)
▼ The transcriptional co-activator with PDZ-binding domain (TAZ) is a transcriptional co-activator and downstream component of the tumor suppressor Hippo pathway that plays critical roles in organ size control, stem cell self-renewal, tumorigenesis and drug resistance. Recently, TAZ has been identified as a novel oncogene that is overexpressed in non-small cell lung cancer (NSCLC) cells and mediates their proliferation, transformation and tumorigenesis. However, the molecular mechanism underlying TAZ-induced tumorigenesis remains largely unknown. In this study, we first established an in vivo xenograft mouse model by overexpressing the constitutively active TAZ-S89A in E10 (mouse) and HBE135 (human) immortalized lung epithelial cells. Next, the gene expression profile of this model was analyzed by performing next-generation sequencing (RNA-seq) which led to identifying several novel genes transcriptionally upregulated by TAZ such as INHBA, KLF5, BMPs, FGFs, etc. Interestingly, we identified PI3K and TGF-ß signaling pathways as mediators of TAZ-induced cell proliferation and transformation, which were inhibited by using small molecule inhibitors specifically targeting these two signaling pathways. In addition, TAZ-induced cell proliferation and transformation were suppressed by disrupting the interaction between TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC.
Subjects/Keywords: TAZ
;
Tumorigenesis
;
Lung Cancer
;
Hippo Pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alharbi, A. (2014). Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/12464
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Alharbi, Adel. “Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
.” 2014. Thesis, Queens University. Accessed January 19, 2021.
http://hdl.handle.net/1974/12464.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Alharbi, Adel. “Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
.” 2014. Web. 19 Jan 2021.
Vancouver:
Alharbi A. Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
. [Internet] [Thesis]. Queens University; 2014. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/1974/12464.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Alharbi A. Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
. [Thesis]. Queens University; 2014. Available from: http://hdl.handle.net/1974/12464
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
12.
Song, Ki Myung.
Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway.
Degree: 2015, University of Toronto
URL: http://hdl.handle.net/1807/70682
► The Hippo pathway regulates cell growth and organ size and dysregulation of the pathway leads to cancer. In mammals, the core Hippo pathway consists of…
(more)
▼ The Hippo pathway regulates cell growth and organ size and dysregulation of the pathway leads to cancer. In mammals, the core Hippo pathway consists of Mst/Lats kinases, which phosphorylate and inhibit transcriptional co-activators, Yap and Taz, by promoting cytoplasmic sequestration. Here, we identify the guanine nucleotide exchange factor (GEF), Arhgef7, or βPix, as a positive Hippo pathway regulator. Upon upstream Hippo signals emanating from cell-cell contact and actin cytoskeletal rearrangements, βPix functions to regulate Yap/Taz localization and activity in a GEF-independent manner. βPix interacts with Yap via the C-terminal KER domain and this physical interaction plays a key role in βPix-mediated Yap/Taz regulation. In normal mammary epithelial cells, Lats kinases are required for βPix function while Mst kinases are not required for Hippo signalling. In breast cancer cells, ectopic expression of βPIX is sufficient to re-couple the Hippo kinase cassette to Yap/Taz, suggesting a possible role as a tumour suppressor.
M.Sc.
Advisors/Committee Members: Attisano, Liliana, Biochemistry.
Subjects/Keywords: Arfgef7; Hippo; Lats; Mst; Yap/Taz; 0487
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Song, K. M. (2015). Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/70682
Chicago Manual of Style (16th Edition):
Song, Ki Myung. “Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway.” 2015. Masters Thesis, University of Toronto. Accessed January 19, 2021.
http://hdl.handle.net/1807/70682.
MLA Handbook (7th Edition):
Song, Ki Myung. “Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway.” 2015. Web. 19 Jan 2021.
Vancouver:
Song KM. Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/1807/70682.
Council of Science Editors:
Song KM. Investigating βPix as a Novel Upstream Regulator of the Hippo Pathway. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/70682
Harvard University
13.
Zhang, Huadi.
SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy.
Degree: PhD, 2017, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061511
► Oncogenic transformation is often accompanied by chromosome instability, an increased rate of chromosome missegregation. The consequent gain or loss of chromosomes—termed aneuploidy—hinders the growth of…
(more)
▼ Oncogenic transformation is often accompanied by chromosome instability, an increased rate of chromosome missegregation. The consequent gain or loss of chromosomes—termed aneuploidy—hinders the growth of most non-cancerous tissues, but is prevalent in tumors. During tumorigenesis, aneuploidy contributes to cellular heterogeneity and may promote downstream mutations, including chromosome rearrangements and oncogene amplification. Cellular mechanisms that safeguard against aneuploidy remain unclear.
The Hippo pathway is a tumor-suppressor mechanism with essential roles in regulating tissue homeostasis. YAP, the downstream effector inhibited by the Hippo pathway, is an oncogenic transcriptional cofactor that promotes proliferation and is frequently amplified in cancers. Upstream regulators of the Hippo pathway and YAP are partially understood.
SPINT2 is a transmembrane protein with extracellular serine protease inhibitor domains and is a negative regulator of various proteases including activators of growth factors. Epigenetic silencing of SPINT2 by promoter hypermethylation is observed in cancers such as medulloblastoma, renal cell carcinoma, and acute myeloid leukemia. Notably, recent findings demonstrate that SPINT2 loss enables cells to tolerate multiple types of stress, including cytokinesis failure and DNA damage. Considering the distinct cellular machineries that respond to these stresses, it is conceivable that SPINT2 may regulate multiple signaling pathways.
In the present dissertation, I delineate SPINT2’s role as a negative regulator of YAP. I demonstrate that SPINT2 limits YAP activity via protease-activated receptors. In addition, using models of chromosome missegregation and aneuploidy, I establish that loss of SPINT2 confers heightened cellular tolerance for aneuploidy.
My findings highlight two intriguing hypotheses regarding cellular processes of cancer development. First, broad-spectrum membrane-anchored protease modulators such as SPINT2 may serve as “convergence points” where a multitude of extracellular signals are regulated for discrete downstream signaling events inside the cell. Second, the tolerance for aneuploidy may be a “built-in” component of oncogenic signaling such as YAP activation, as opposed to requiring separate cellular mechanisms. The aneuploid state of tumors, therefore, may be an integral output of intra- and extra-cellular oncogenic signaling, and may serve as a feedforward process that enhances further genomic instability during tumorigenesis.
Medical Sciences
Advisors/Committee Members: Toker, Alex (advisor), Gaudet, Suzanne (committee member), Muthuswamy, Senthil (committee member), Varelas, Xaralabos (committee member).
Subjects/Keywords: Extracellular Proteolysis; Hippo Signaling; Chromosome Instability
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, H. (2017). SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061511
Chicago Manual of Style (16th Edition):
Zhang, Huadi. “SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy.” 2017. Doctoral Dissertation, Harvard University. Accessed January 19, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061511.
MLA Handbook (7th Edition):
Zhang, Huadi. “SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy.” 2017. Web. 19 Jan 2021.
Vancouver:
Zhang H. SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy. [Internet] [Doctoral dissertation]. Harvard University; 2017. [cited 2021 Jan 19].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061511.
Council of Science Editors:
Zhang H. SPINT2 Suppresses Hippo Effector YAP and Limits Cellular Tolerance for Aneuploidy. [Doctoral Dissertation]. Harvard University; 2017. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061511
University of Guelph
14.
Luu, Anita.
An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis.
Degree: MS, Department of Biomedical Sciences, 2016, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9968
► Osteosarcoma (OSA) is the most common bone tumor in canines and has high metastatic potential. Evidence suggests that TGFβ and TAZ, either independently or in…
(more)
▼ Osteosarcoma (OSA) is the most common bone tumor in canines and has high metastatic potential. Evidence suggests that TGFβ and TAZ, either independently or in combination, could potentially drive OSA progression. However, this role has not been explored in canine OSA. In this study, the prognostic value of TGFβ-TAZ signaling was explored in a tissue microarray. It was determined that the levels of active TGFβ signaling alone, or in combination with TAZ levels suggest an earlier time to metastasis. Furthermore, in vitro expression of metastasis-associated genes and cell migration following TAZ knockdown with/without TGFβ treatment was evaluated. In the absence of TGFβ and high levels of TAZ, cell migration was impaired in a metastatic OSA cell line, but not in two primary OSA cell lines. These findings suggest that TGFβ-TAZ signaling could have a role in promoting OSA metastasis. Additional studies are required to validate the importance of this crosstalk.
Advisors/Committee Members: Viloria-Petit, Alicia (advisor).
Subjects/Keywords: TGFβ signaling; canine osteosarcoma; Metastasis; Hippo signaling
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Luu, A. (2016). An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9968
Chicago Manual of Style (16th Edition):
Luu, Anita. “An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis.” 2016. Masters Thesis, University of Guelph. Accessed January 19, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9968.
MLA Handbook (7th Edition):
Luu, Anita. “An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis.” 2016. Web. 19 Jan 2021.
Vancouver:
Luu A. An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis. [Internet] [Masters thesis]. University of Guelph; 2016. [cited 2021 Jan 19].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9968.
Council of Science Editors:
Luu A. An investigation of the role of the TGFbeta-TAZ signaling crosstalk in canine osteosarcoma metastasis. [Masters Thesis]. University of Guelph; 2016. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9968
15.
Weldrick, Jonathan.
Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
.
Degree: 2019, University of Ottawa
URL: http://hdl.handle.net/10393/39809
► Background: Extensive research has characterized the embryonic development of a four-chambered heart in mammals. After birth, mammalian cardiomyocytes undergo a transition characterized by a final…
(more)
▼ Background:
Extensive research has characterized the embryonic development of a four-chambered heart in mammals. After birth, mammalian cardiomyocytes undergo a transition characterized by a final cell cycle with nuclear division (karyokinesis) in the absence of cytoplasmic division (cytokinesis), generating mature binucleated cardiomyocytes. Downregulation of pro-proliferative signaling and epigenetic changes permanently ‘lock’ cardiomyocytes out of the cell cycle, and nearly all subsequent growth is accomplished via cellular hypertrophy. Before this transition, cardiomyocytes exhibit robust proliferative potential, but afterward are unable to divide.
Rationale & Hypothesis:
Recent evidence suggests that non-coding RNAs influence early neonatal cardiac development and hypertrophy. We hypothesize that transient expression of regulatory miRNAs may impact the neonatal heart’s transition from proliferation to hypertrophy.
Results:
Cardiac mRNA and miRNA were systematically analyzed using microarrays to identify targets that were transiently and significantly changing after birth. Through our analysis we identified three primary ontogenies significantly changing: metabolism, extracellular matrix remodeling, and cell cycle regulation.
Global analysis of micro-RNA expression patterns during perinatal heart development identified miR-205 as a novel candidate for modulating cardiomyocyte maturation. We observed miR-205 expression undergoing a 20-fold increase from 1-day postpartum (1D) to 5D, returning to prenatal levels by 10D. It is expressed in cardiomyocytes of the epicardium, the primary location of fetal cardiomyocyte proliferation. MiR-205 targets two important cell cycle regulators: Pten phosphatase of the PI3K/AKT pathway, and Yap1 in the Hippo pathway. Both pathways have proven to be essential for proper heart development. Previous research showed that germline deletion of miR-205 results in death at 5D.
To define its role in the heart, we generated an αMHC-Cre postnatal miR-205 cardiac-specific deletion mouse model. Systematic characterization of miR-205-/- hearts confirmed miR-205’s interaction with Pten and Yap1 by western blot and immunohistochemistry. Postnatal miR-205-/- hearts exhibit Hippo pathway dysregulation, increased cardiomyocyte number, more actively cycling cardiomyocytes beyond 7D, and no difference in binucleation.
We also generated a DOX-inducible cardiac-specific miR-205 over-expression mouse model. Perinatal miR-205OE hearts expedited the transitional period, with more cardiomyocytes present at 5D and no difference at 14D. These hearts show increased Hippo signaling immediately after birth, suggesting compensatory mechanisms to ensure sufficient cardiomyocyte number.
Conclusions:
Our data strongly supports miR-205 as a regulator of cardiomyocyte maturation in the neonatal heart, by promoting the neonatal cardiomyocyte transition from hyperplastic to hypertrophic growth. In turn, miR-205’s antiproliferative properties originate in part from suppressing the expression of Pten…
Subjects/Keywords: Neonatal;
Development;
MiRNA;
Cardiac;
Hippo;
Proliferation
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Weldrick, J. (2019). Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/39809
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Weldrick, Jonathan. “Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
.” 2019. Thesis, University of Ottawa. Accessed January 19, 2021.
http://hdl.handle.net/10393/39809.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Weldrick, Jonathan. “Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
.” 2019. Web. 19 Jan 2021.
Vancouver:
Weldrick J. Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
. [Internet] [Thesis]. University of Ottawa; 2019. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/10393/39809.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Weldrick J. Gene Expression Analysis of the Perinatal Heart and the Identification of MiR-205 as a Regulator of Cardiomyocyte Maturation
. [Thesis]. University of Ottawa; 2019. Available from: http://hdl.handle.net/10393/39809
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston College
16.
Thomas, Adam Michael.
The Eternal Law in Augustine's Early Investigation of
Justice.
Degree: PhD, Political Science, 2016, Boston College
URL: http://dlib.bc.edu/islandora/object/bc-ir:107191
► In my dissertation I seek to contribute to the revival of interest in Augustine’s political thought by attempting to uncover his doctrine of eternal law.…
(more)
▼ In my dissertation I seek to contribute to the revival
of interest in Augustine’s political thought by attempting to
uncover his doctrine of eternal law. While absent from his mature
writings, including the City of God, this doctrine is central to
the investigation of justice in Augustine’s early writings. After
considering Augustine’s summary of this early investigation in the
Confessions, the most surprising feature of which is Augustine’s
insistence on the importance of specifically political questions to
his mature understanding of justice, I take up the two treatments
of eternal law. In the dialogue On Free Choice, the eternal law is
contrasted with the temporal law and is understood in terms of the
fundamental command to “order,” which means in the first place
wisdom, but also “right and honorable” action. In the
anti-Manichean polemic Contra Faustum, the eternal law is presented
as the will of God that commands the preservation of the natural
order, which means that actions are truly just insofar as they
conduce to “mortal health.” I argue that these two discussions of
eternal law indicate the limitations of any kind of “higher law”
doctrine. On Free Choice demonstrates the difficulty of breaking
free of the guidance of temporal law and its harmonization of the
demands of eternal and temporal law depends on an understanding of
moral virtue whose independence is rather assumed than proven.
Contra Faustum shows that the natural ends of self-preservation,
procreation, and civic peace are only the beginning points of moral
reasoning, since the pursuit of those ends is governed by further
moral criteria that cannot easily be understood in terms of nature.
In the end, then, I argue that the doctrine of eternal law, while
illuminating a great deal about the problems of politics and
morality as Augustine encountered them, points to the crucial
importance of the question of human virtue and of acquiring the
prudence that provides for this virtue in light of the necessary
limitations of political life. It is probably for this reason that
Augustine does not return to the doctrine in his later writings and
does not rely on it in his reconciliation of the two cities in the
City of God.
Advisors/Committee Members: Robert C. Bartlett (Thesis advisor).
Subjects/Keywords: Eternal law; Augustine, Saint, Bishop of Hippo
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thomas, A. M. (2016). The Eternal Law in Augustine's Early Investigation of
Justice. (Doctoral Dissertation). Boston College. Retrieved from http://dlib.bc.edu/islandora/object/bc-ir:107191
Chicago Manual of Style (16th Edition):
Thomas, Adam Michael. “The Eternal Law in Augustine's Early Investigation of
Justice.” 2016. Doctoral Dissertation, Boston College. Accessed January 19, 2021.
http://dlib.bc.edu/islandora/object/bc-ir:107191.
MLA Handbook (7th Edition):
Thomas, Adam Michael. “The Eternal Law in Augustine's Early Investigation of
Justice.” 2016. Web. 19 Jan 2021.
Vancouver:
Thomas AM. The Eternal Law in Augustine's Early Investigation of
Justice. [Internet] [Doctoral dissertation]. Boston College; 2016. [cited 2021 Jan 19].
Available from: http://dlib.bc.edu/islandora/object/bc-ir:107191.
Council of Science Editors:
Thomas AM. The Eternal Law in Augustine's Early Investigation of
Justice. [Doctoral Dissertation]. Boston College; 2016. Available from: http://dlib.bc.edu/islandora/object/bc-ir:107191
Boston University
17.
Mahoney, John Edmund.
The role of Yap in lung development.
Degree: PhD, Pathology & Laboratory Medicine, 2014, Boston University
URL: http://hdl.handle.net/2144/14692
► The mechanisms by which epithelial progenitor cells integrate local signals to balance proliferation with differentiation and regulate patterning during lung organogenesis are still poorly understood.…
(more)
▼ The mechanisms by which epithelial progenitor cells integrate local signals to balance proliferation with differentiation and regulate patterning during lung organogenesis are still poorly understood. The Hippo pathway and its transcription co-activator Yap have recently emerged as major regulators of progenitor cell expansion and differentiation in development and cancer. Here we investigated the role of Yap signaling in the cellular and molecular events associated with lung epithelial morphogenesis and differentiation. We provide evidence that when airway epithelial tubules are forming and branching, a nuclear to cytoplasmic shift of Yap marks the boundary between the progenitors of the distal lung and the airway compartment. At this transition zone, Yap specifies a transcriptional program that controls the expression of Sox2, restricting distal gene expression and initiating an airway progenitor cell program key to generate the airway epithelium and its branched tubular structures. In Yap deficient mice, epithelial progenitors are unable to properly respond to local Tgf beta-induced cues to control levels and distribution of Sox2, resulting in expansion of the distal epithelial compartment and inability to form airways. Moreover, we show that Yap levels and phosphorylation status play a major role in regulating differentiation of airway progenitors later in development and in adult life. Analysis of YAP-interacting partners in adult airway progenitors by Mass Spectroscopy suggests phosphorylated Yap interactions with ciliome proteins. Our study reveals a crucial role for Yap in specification and differentiation of airway progenitors likely to be also relevant in regeneration-repair of the adult airway epithelium.
Subjects/Keywords: Developmental biology; Airway; Hippo; Lung; Yap
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mahoney, J. E. (2014). The role of Yap in lung development. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/14692
Chicago Manual of Style (16th Edition):
Mahoney, John Edmund. “The role of Yap in lung development.” 2014. Doctoral Dissertation, Boston University. Accessed January 19, 2021.
http://hdl.handle.net/2144/14692.
MLA Handbook (7th Edition):
Mahoney, John Edmund. “The role of Yap in lung development.” 2014. Web. 19 Jan 2021.
Vancouver:
Mahoney JE. The role of Yap in lung development. [Internet] [Doctoral dissertation]. Boston University; 2014. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/2144/14692.
Council of Science Editors:
Mahoney JE. The role of Yap in lung development. [Doctoral Dissertation]. Boston University; 2014. Available from: http://hdl.handle.net/2144/14692
Boston University
18.
Mueller, Kaly Alyse.
The Hippo pathway in liver regeneration and tumorigenesis.
Degree: MS, Medical Sciences, 2014, Boston University
URL: http://hdl.handle.net/2144/14680
► The Hippo signaling pathway has been implicated in both mammalian organ size regulation, as well as tumor suppression. Specifically, the Hippo pathway plays a critical…
(more)
▼ The Hippo signaling pathway has been implicated in both mammalian organ size regulation, as well as tumor suppression. Specifically, the Hippo pathway plays a critical role regulating the activity of transcriptional co-activator, and downstream effector, Yes-associated protein (YAP), which modulates pro-proliferative transcriptional elements. Recent investigations have demonstrated that this pathway is activated in non-regenerating livers and its inhibition leads to liver overgrowth and tumorigenesis. The majority of the existing evidence regarding the role of the Hippo pathway in hepatocyte proliferation is based on in vitro studies and knock-out animal models. However, the role of the Hippo pathway during the natural process of liver regeneration, remains unknown. Here alterations in the Hippo signaling pathway were investigated, namely its interaction with angiomotin-like 2 (AmotL2) and Set7, during liver regeneration using a 70% rat partial hepatectomy (PH) model. Overall, results indicated no significant difference between AmotL2 levels in control and regenerating tissue at various time points during liver regeneration. No significant alterations in YAP methylation during liver regeneration were found compared to control tissue. In the end, results regarding the role of both AmotL2 and Set7 provided inconclusive evidence about their roles during the regenerative process.
Given the role of the Hippo pathway in hepatocyte proliferation, a hypothesis was made that this pathway may play a role in pediatric liver tumors. YAP localization was evaluated using immunohistochemical analysis in tumor sections from patients with hepatoblastoma or hepatocellular carcinoma. Once again, the results were inconclusive at the time of the preparation of this manuscript due to technical difficulties in achieving satisfactory staining of the specimens.
Further studies will be directed at elucidating the role of the Hippo pathway during liver regeneration as well as developing better conditions for the immunohistochemical staining of human liver specimens.
Subjects/Keywords: Biochemistry; Hippo; Liver; Regeneration; Tumorigenesis; YAP
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mueller, K. A. (2014). The Hippo pathway in liver regeneration and tumorigenesis. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/14680
Chicago Manual of Style (16th Edition):
Mueller, Kaly Alyse. “The Hippo pathway in liver regeneration and tumorigenesis.” 2014. Masters Thesis, Boston University. Accessed January 19, 2021.
http://hdl.handle.net/2144/14680.
MLA Handbook (7th Edition):
Mueller, Kaly Alyse. “The Hippo pathway in liver regeneration and tumorigenesis.” 2014. Web. 19 Jan 2021.
Vancouver:
Mueller KA. The Hippo pathway in liver regeneration and tumorigenesis. [Internet] [Masters thesis]. Boston University; 2014. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/2144/14680.
Council of Science Editors:
Mueller KA. The Hippo pathway in liver regeneration and tumorigenesis. [Masters Thesis]. Boston University; 2014. Available from: http://hdl.handle.net/2144/14680
19.
Jagannathan, Radhika.
Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins.
Degree: PhD, Biology and Biomedical Sciences: Molecular Cell Biology, 2014, Washington University in St. Louis
URL: https://openscholarship.wustl.edu/etd/1239
► The highly conserved Hippo kinase cascade is critical for both regulation of organ size in development and tumor suppression. Several mechanisms, such as cell-cell…
(more)
▼ The highly conserved
Hippo kinase cascade is critical for both regulation of organ size in development and tumor suppression. Several mechanisms, such as cell-cell contact in vitro and organ size in vivo, have been implicated in the activation of the
Hippo pathway, leading to inactivation of the YAP/TAZ transcriptional coactivators and growth arrest. Previous work from our lab has identified the Ajuba LIM proteins as novel negative regulators of the
Hippo pathway in both Drosophila and mammals. However, the mechanism by which the Ajuba LIM proteins prevent
Hippo pathway activity is not known. Using contact inhibition of proliferation as a functional assay of
Hippo pathway activity, we find that the Ajuba LIM proteins bind to the Ndr-kinase Lats1/2 and inhibit
Hippo pathway mediated inactivation of YAP only in low density, proliferating cells, suggesting that the Ajuba LIM proteins function to keep the
Hippo pathway off in contexts where cell proliferation is needed, but are unable to prevent activation of the pathway by signals such as cell density. We demonstrate that the Ajuba LIM proteins enhance association of the core kinase complex, and, using a panel of LIM domain mutants of the Ajuba LIM protein, LIMD1, identify the domains required for sequestering active Lats2 in the core kinase complex. Using Drosophila wing size as an in vivo read-out of
Hippo activity, we find that only the domain mutants that increase complex association suppress
Hippo-mediated YAP inactivation. We also determine the role of subcellular localization in Ajuba LIM-mediated inhibition of the
Hippo pathway. It has previously been shown that targeting the complex to the plasma membrane, using a membrane targeted Mob1, can lead to its activation; interestingly, we find that LIMD1 is unable to associate with or enhance the association of this membrane-targeted complex. Conversely, targeting LIMD1 to the plasma membrane also abrogates its ability to bind to, and enhance the association of, the cytoplasmic core kinase complex. Given that LIMD1 and the
Hippo complex are both recruited to the plasma membrane in high density, growth-arrested cells, these results provide a model for Ajuba LIM-mediated inhibition of
Hippo pathway signaling, in which the Ajuba LIM proteins physically interact with the core kinase complex in the cytoplasm of low-density, proliferating cells, thereby preventing inactivation of YAP and premature growth arrest.
Advisors/Committee Members: Gregory D. Longmore.
Subjects/Keywords: Ajuba LIM; Contact Inhibition; Hippo Pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jagannathan, R. (2014). Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/1239
Chicago Manual of Style (16th Edition):
Jagannathan, Radhika. “Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins.” 2014. Doctoral Dissertation, Washington University in St. Louis. Accessed January 19, 2021.
https://openscholarship.wustl.edu/etd/1239.
MLA Handbook (7th Edition):
Jagannathan, Radhika. “Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins.” 2014. Web. 19 Jan 2021.
Vancouver:
Jagannathan R. Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2014. [cited 2021 Jan 19].
Available from: https://openscholarship.wustl.edu/etd/1239.
Council of Science Editors:
Jagannathan R. Negative Regulation of the Hippo Pathway by the Ajuba LIM Proteins. [Doctoral Dissertation]. Washington University in St. Louis; 2014. Available from: https://openscholarship.wustl.edu/etd/1239
Penn State University
20.
Deng, Yaoting.
Regulation of Hippo Signaling for Growth Control.
Degree: 2014, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/23417
► In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ…
(more)
▼ In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ function. The mechanisms that regulate these crucial processes provide insight into diseases, such as cancer. The
Hippo (Hpo) signaling regulates cell number mainly by inhibiting cell proliferation and promoting cell apoptosis, and this signaling is highly conserved from Drosophila to mammals. Hpo is the key kinase of Hpo signaling; however, the way in which Hpo kinase activity is regulated remains less understood. In this project, I investigated how Hpo kinase is activated and regulated by upstream molecules both in vivo and in vitro. I found that Hpo dimerization could facilitate its activation by auto-phosphorylation. Moreover, membrane association appears to increase Hpo dimerization efficiency, and upstream molecules Expanded/Merlin/Kibra promote Hpo membrane association. Therefore, both dimerization and membrane association are critical for Hpo kinase to be activated. This mechanism provides essential insight to reveal the mystery that how upstream molecules transduce signal to Hpo signaling.
In another project, I investigated Yap1 (a major downstream effector of mammalian Hpo signaling) activity regulation in mammalian pancreatic beta β-cells under free fatty acids (FFAs) treatment. Mammalian pancreatic β-cells are responsible for the production of insulin and therefore play a pivotal role in development and glucose homeostasis. Among many factors, high concentrations of saturated free fatty acids (FFAs) such as palmitate are known to have a negative effect on β-cell viability, which might induce type 2 diabetes. In this study, I demonstrated that Hpo signaling effector Yap1 plays a crucial role in regulating β-cell survival under FFA treatment. I found that Yap1 is activated through F-actin accumulation in a time-delayed manner to enhance β-cells viability during palmitate-induced apoptosis. Moreover, Connective Tissue Growth Factor (CTGF), one of the downstream targets of Yap1, was identified to repress palmitate-induced β-cell apoptosis. These discoveries support a model in which Yap1 could positively regulate β-cell survival under FFA treatment, and this model might lead to the development of new strategies for potential treatment of diabetes.
Advisors/Committee Members: Zhi Chun Lai, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Melissa Rolls, Committee Member, Pamela Hankey Giblin, Committee Member, Richard W Ordway, Committee Member, Wendy Hanna Rose, Committee Member, Yanming Wang, Committee Member.
Subjects/Keywords: Hippo pathway; Hippo; transphosphorylation; dimerization; Merlin; Expanded; Kibra; FFA; β-cells; Yap; F-actin; apoptosis
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Deng, Y. (2014). Regulation of Hippo Signaling for Growth Control. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23417
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Thesis, Penn State University. Accessed January 19, 2021.
https://submit-etda.libraries.psu.edu/catalog/23417.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Web. 19 Jan 2021.
Vancouver:
Deng Y. Regulation of Hippo Signaling for Growth Control. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Jan 19].
Available from: https://submit-etda.libraries.psu.edu/catalog/23417.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Deng Y. Regulation of Hippo Signaling for Growth Control. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23417
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
Yanai, Hiroshi.
Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究.
Degree: 博士（学術）, 2015, Kyoto Institute of Technology / 京都工芸繊維大学
URL: http://hdl.handle.net/10212/2251
► Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF)…
(more)
▼ Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF) as a bait. DREF is a transcription factor that regulates proliferation-related genes in Drosophila. It is known that overexpression of dMLF in the wing imaginal discs through the engrailed-GAL4 driver causes an atrophied wing phenotype associated with the induction of apoptosis. However, the precise mechanisms involved have yet to be clarified. Here, I found the atrophied phenotype to be suppressed by loss-of-function mutation of Drosophila Jun N-terminal kinase (JNK), basket (bsk). Overexpression of dMLF induced ectopic JNK activation in the wing disc monitored with the puckered-lacZ reporter line, resulting in induction of apoptosis. The DREF-binding consensus DRE sequence could be shown to exist in the bsk promoter. Chromatin immunoprecipitation assays in S2 cells with anti-dMLF IgG and quantitative real-time PCR revealed that dMLF binds specifically to the bsk promoter region containing the DRE sequence. Furthermore, using a transient luciferase expression assay, I provide evidence that knockdown of dMLF reduced bsk gene promoter activity in S2 cells. Finally, I show that dMLF interacts with DREF in vivo. Together, these data indicate that dMLF acts with DREF to stimulate the bsk promoter and consequently activates the JNK pathway to promote apoptosis. In addition, the DRE/DREF transcriptional regulatory system has been demonstrated to activate a wide variety of genes with various functions. In Drosophila, the Hippo (Hpo) pathway is known to suppress cell proliferation by inducing apoptosis and cell cycle arrest through inactivation of Yorkie, a transcription co-activator. Here, I also carried out analyses of transcriptional regulation of the hippo (hpo) gene in Drosophila. By this analysis, I revealed that DREF is required for transcriptional activation of the hpo gene to positively control the Hippo pathway. Altogether, the DRE/DREF pathway is involved in both the JNK and the Hpo pathway, and appears to play an important role in induction of apoptosis.
Subjects/Keywords: Drosophila; MLF; DREF; JNK; basket; Hippo; hippo; Yorkie; apoptosis; wing imaginal discs; eye imaginal discs
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yanai, H. (2015). Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究. (Thesis). Kyoto Institute of Technology / 京都工芸繊維大学. Retrieved from http://hdl.handle.net/10212/2251
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yanai, Hiroshi. “Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究.” 2015. Thesis, Kyoto Institute of Technology / 京都工芸繊維大学. Accessed January 19, 2021.
http://hdl.handle.net/10212/2251.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yanai, Hiroshi. “Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究.” 2015. Web. 19 Jan 2021.
Vancouver:
Yanai H. Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究. [Internet] [Thesis]. Kyoto Institute of Technology / 京都工芸繊維大学; 2015. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/10212/2251.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yanai H. Cell biological and genetical studies on Drosophila myeloid leukemia factor (dMLF) and DRE/DREF transcriptional regulatory pathway : ショウジョウバエ骨髄性白血病因子dMLFとDRE/DREF転写制御経路の細胞生物学的及び遺伝学的研究. [Thesis]. Kyoto Institute of Technology / 京都工芸繊維大学; 2015. Available from: http://hdl.handle.net/10212/2251
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
22.
Martin, Alexandre.
La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2019, Paris Sciences et Lettres (ComUE)
URL: http://www.theses.fr/2019PSLET002
► STK38 est une sérine/thréonine kinase appartenant à la voie de signalisation Hippo et possédant de multiples fonctions dans des cellules tant normales que cancéreuses. De…
(more)
▼ STK38 est une sérine/thréonine kinase appartenant à la voie de signalisation Hippo et possédant de multiples fonctions dans des cellules tant normales que cancéreuses. De précédents travaux, réalisés par notre équipe et par des collaborateurs, ont permis d’identifier le rôle central de STK38 dans la progression du cycle cellulaire, la duplication centrosomale, l’apoptose, ainsi que l’activité transcriptionnelle. De façon importante, STK38 a été caractérisée comme agissant en aval des protéines Ral (des effecteurs de la famille de protéine Ras) dans deux processus cellulaires nécessaires au maintien de l’homéostasie cellulaire se trouvant souvent dérégulés dans les cellules cancéreuses. D’un côté, STK38 établis un pont à la croisée des voies de signalisation Ral-Ral et Hippo en régulant positivement l’autophagie. D’un autre côté, STK38 est indispensable à la résistance des cellules cancéreuses à l’anoïkis lors du détachement de la matrice extracellulaire. Ces observations montrent l’implication de STK38 dans des processus cellulaires, semblant n’avoir aucun lien entre eux, régulas par diverses cascades de signalisation.Dans ce travail, nous avons découvert que STK38 interagit avec différents partenaires protéiques, pour un total de plus 250 protéines identifiées, en fonction du contexte cellulaire. Dans le détail, nous avons trouvé que STK38 augmente son association avec des protéines cytoplasmiques lors de l’autophagie induite par carence nutritive, alors que STK38 augmente son association avec des partenaires nucléaires, au détriment de partenaires cytoplasmiques, lors du détachement à la matrice extracellulaire. Nous avons découvert que STK38 navigue entre le noyau et le cytoplasme, en fonction du contexte cellulaire, sous la dépendance de XPO1. Nous avons caractérisé STK38 comme le tout premier activateur de XPO1 via la phosphorylation du domaine auto-inhibiteur de XPO1, phosphorylation nécessaire à la présentation de sa région de liaison du cargo. En plus de décider de sa propre disponibilité subcellulaire, STK38 régule également l’export nucléaire d’effecteurs protéiques, telles que Beclin1, YAP1 et Centrin, effecteurs ayant été caractérisé comme impliqués dans certaines fonctions liées à STK38.Ces résultats révèlent que de multiples fonctions cellulaires, semblant régulées par une unique protéine, une kinase dans notre cas, STK38, peuvent en fait être expliquées par un mécanisme moléculaire unique : réguler la distribution subcellulaire d’effecteurs clés en modulant l’activité exportatrice de XPO1 via la phosphorylation de sa région auto-inhibitrice.
The Hippo pathway STK38 serine/threonine protein kinase is implicated in multifarious biological processes in both normal and cancer cells. Previous work performed by our team and collaborators have identified the central role of STK38 in cell cycle progression, centrosome duplication, apoptosis, and transcriptional activity. Importantly, STK38 has been characterized to act downstream of the Ral proteins (effectors of Ras proteins family) in two cellular…
Advisors/Committee Members: Camonis, Jacques (thesis director).
Subjects/Keywords: Cancer; Stk38; Xpo1; Autophagie; Yap; Hippo; Cancer; Stk38; Xpo1; Autophagy; Yap; Hippo; 570
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Martin, A. (2019). La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1. (Doctoral Dissertation). Paris Sciences et Lettres (ComUE). Retrieved from http://www.theses.fr/2019PSLET002
Chicago Manual of Style (16th Edition):
Martin, Alexandre. “La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1.” 2019. Doctoral Dissertation, Paris Sciences et Lettres (ComUE). Accessed January 19, 2021.
http://www.theses.fr/2019PSLET002.
MLA Handbook (7th Edition):
Martin, Alexandre. “La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1.” 2019. Web. 19 Jan 2021.
Vancouver:
Martin A. La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1. [Internet] [Doctoral dissertation]. Paris Sciences et Lettres (ComUE); 2019. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2019PSLET002.
Council of Science Editors:
Martin A. La kinase STK38 contrôle la distribution subcellulaire de partenaires en phosphorylant le domaine d'auto-inhibition de XPO1 : The STK38 kinase regulates the subcellular distribution of downstream partners by phosphorylating the auto-inhibitory domain of XPO1. [Doctoral Dissertation]. Paris Sciences et Lettres (ComUE); 2019. Available from: http://www.theses.fr/2019PSLET002
23.
Philippe, Chloe.
Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR.
Degree: Docteur es, Biologie cellulaire et physiopathologie, 2016, Bordeaux
URL: http://www.theses.fr/2016BORD0454
► L’AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) est un intermédiaire de la voie de biosynthèse des purines. A des concentrations importantes, ce métabolite a un effet cytotoxique sur les…
(more)
▼ L’AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) est un intermédiaire de la voie de biosynthèse des purines. A des concentrations importantes, ce métabolite a un effet cytotoxique sur les cellules cancéreuses aneuploïdes, c’est-à-dire contenant un nombre anormal de chromosome. Or,90% des tumeurs solides sont aneuploïdes. Les mécanismes responsables de cette cytotoxicité doivent donc être mieux étudiés pour une utilisation éventuelle en thérapie anti-cancéreuse.Dans la littérature, l’effet de l’AICAR est expliqué par son rôle mimétique de l’AMP sur l’AMPK.Cependant, certaines données de la littérature et du laboratoire laissent penser que l’inhibition de la croissance par l’AICAR peut impliquer plusieurs types de mécanismes dont certains sont dépendantsde l’AMPK et d’autres indépendants. L’identification des cibles de l’AICAR alternatives à l’AMPK estdonc nécessaire pour une meilleure compréhension de ses effets.Dans ce projet, j’ai pu confirmer la présence d’autres cibles de l’AICAR indépendantes de l’AMPKet responsables de son effet cytotoxique. Grâce à une approche transcriptomique, j’ai montré un effetde l’AICAR sur l’expression et l’activation de LATS1 et LATS2 (large tumor suppressor 1 and 2). Ces protéines kinases fond partie du core enzymatique de la voie HIPPO, dont le rôle en cancérologie est fondamental. Les effecteurs finaux de cette voie sont YAP et TAZ, deux cofacteurs de transcription,aussi régulés par l’AICAR. J’ai pu montrer que la cytotoxicité de l’AICAR est due en partie à l’activation de cette voie. Depuis la découverte récente de la voie HIPPO, de nombreuses études visent à identifier des molécules permettant l’inhibition directe de cette voie. L’AICAR s’avère être une molécule puissante dans le cadre d’une thérapie anticancéreuse ciblant la voie HIPPO.
AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) is an intermediate of the purine biosynthesis pathway. At high concentrations, this metabolite has a cytotoxic effect on aneuploid cancer cells that is cells containing an abnormal chromosome number. However, 90% of solid tumorsare aneuploid. The mechanisms responsible for this cytotoxicity should be better studied for possible use in anti-cancer therapy.In the literature, the effect of AICAR is explained by its AMP mimetic role on the AMPK. However,some literature and laboratory data suggest that AICAR growth inhibition may involve several types of mechanisms, some of which are dependent and other independent of AMPK. Therefore, the identification of AMPK alternative targets is necessary for a better understanding the AICAR effects. In this project, I was able to confirm the presence of other AICAR targets independent of AMPK and responsible for its cytotoxic effect. Using a transcriptomic approach, I showed an effect of AICAR on the expression and activation of LATS1 and LATS2 (large tumor suppressor 1 and 2). These proteinkinases form part of the enzymatic nucleus of the HIPPO pathway, whose role in oncology is fundamental. The effectors of this pathway are YAP and TAZ, two…
Advisors/Committee Members: Moenner, Michel (thesis director).
Subjects/Keywords: AICAR; Voie HIPPO; Effets cytotoxiques; AMPK; AICAR; HIPPO pathway; Cytotoxic effect; AMPK
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Philippe, C. (2016). Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR. (Doctoral Dissertation). Bordeaux. Retrieved from http://www.theses.fr/2016BORD0454
Chicago Manual of Style (16th Edition):
Philippe, Chloe. “Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR.” 2016. Doctoral Dissertation, Bordeaux. Accessed January 19, 2021.
http://www.theses.fr/2016BORD0454.
MLA Handbook (7th Edition):
Philippe, Chloe. “Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR.” 2016. Web. 19 Jan 2021.
Vancouver:
Philippe C. Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR. [Internet] [Doctoral dissertation]. Bordeaux; 2016. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2016BORD0454.
Council of Science Editors:
Philippe C. Modulation de la voie HIPPO par un métabolite aux propriétés anti-tumorales : l'AICAR : Modulation of the HIPPO pathway by a metabolite with anti-tumor properties : AICAR. [Doctoral Dissertation]. Bordeaux; 2016. Available from: http://www.theses.fr/2016BORD0454
University of Melbourne
24.
DENT, LUCAS.
Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster.
Degree: 2015, University of Melbourne
URL: http://hdl.handle.net/11343/55376
► Background: The Hippo signalling pathway was discovered is Drosophila melanogaster and is a conserved regulator of tissue growth in animals. This pathway is also deregulated…
(more)
▼ Background: The Hippo signalling pathway was discovered is Drosophila melanogaster and is a conserved regulator of tissue growth in animals. This pathway is also deregulated in human cancers. The Hippo pathway consists of upstream growth-suppressing proteins that work together to restrict the activity of the growth promoting protein, Yorkie (Yki). Despite its importance in disease and development, the complete set of signals that regulate the Hippo pathway remain to be determined.
Approach and aims: I wanted to improve our understanding of the mechanisms controlling the Hippo pathway in Drosophila. To do this, I considered the results of a proteomic screen to identify proteins that bind to the Hippo (Hpo) kinase. Prominent amongst these proteins were Pak-interacting exchange factor (Pix), and G-protein coupled receptor kinase-interacting protein (Git). Pix, is a conserved rho-type guanine nucleotide exchange factor (RhoGEF), and is homologous to Beta-PIX and Alpha-PIX in mammals. Git, is the Drosophila homolog of the mammalian GIT1 and GIT2 proteins, and acts as an Arf-GTPase activating protein (ArfGAP). Pix and Git also heterodimerise with each other to form an oligomeric scaffold and facilitate sterile 20-like kinase activation. In this thesis, I used genetics and biochemistry approaches to investigate the following questions: 1) Do Pix and Git regulate the activity of the Hippo pathway? 2) Do Pix and Git regulate the activation of the Hpo kinase? 3) Does the Pix-Git complex have non-growth roles in epithelial development and are these related to Hippo signalling?
Results: 1) I found that Pix and Git co-operate to modulate tissue growth through the Hippo pathway. Mutation of pix and git did not produce growth phenotypes, however mutating either of these genes in conjunction with other Hippo pathway regulators resulted in striking tissue overgrowth. Consistent with this, simultaneous expression of pix, git and hpo, severely limits tissue growth. These effects occur through the Hippo signalling pathway, as silencing pix increased Yki activity. Moreover, Pix and Git form a physical complex with Hpo, and epistasis experiments show that pix and git function upstream of hpo in growth control.
2) I showed that the Pix-Git complex controls growth by directly regulating the activity of the Hpo kinase. Co-expression of pix and git promoted Hpo homodimerisation, and increased Hippo autophosphorylation at its activation loop. Pix and Git appear to serve as scaffolds to recruit and activate Hpo, as their enzymatic domains are dispensable for Hpo activation.
3) Loss of pix and git resulted in a range of epithelial defects that were not directly growth related. These include defects in the coordinated migration of epithelial cells, the maintenance of basal filamentous actin, and disruption of epithelial polarity in developing egg chambers. Genetic interaction experiments showed that the cell migration phenotypes of pix and git are related to signalling via the sterile 20-kinase Pak, and not Hippo signalling.
…
Subjects/Keywords: tissue growth; epithelia; epithelial development; Drosophila; Drosophila melanogaster; Hippo signaling; Hippo pathway; Hippo; Pix; Git; Beta-Pix; Git1; Git2; dPix, dGit; Yorkie
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
DENT, L. (2015). Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/55376
Chicago Manual of Style (16th Edition):
DENT, LUCAS. “Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster.” 2015. Doctoral Dissertation, University of Melbourne. Accessed January 19, 2021.
http://hdl.handle.net/11343/55376.
MLA Handbook (7th Edition):
DENT, LUCAS. “Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster.” 2015. Web. 19 Jan 2021.
Vancouver:
DENT L. Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster. [Internet] [Doctoral dissertation]. University of Melbourne; 2015. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/11343/55376.
Council of Science Editors:
DENT L. Combining proteomics and functional genetics to find new regulators of tissue growth and development in Drosophila melanogaster. [Doctoral Dissertation]. University of Melbourne; 2015. Available from: http://hdl.handle.net/11343/55376
25.
Grampa, Valentina.
Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères.
Degree: Docteur es, Biologie cellulaire et moléculaire, 2015, Sorbonne Paris Cité
URL: http://www.theses.fr/2015USPCB099
► Les ciliopathies sont un groupe de maladies génétiques multi-systémiques liées à un dysfonctionnement du cil primaire, une structure sensorielle présente à la surface des cellules…
(more)
▼ Les ciliopathies sont un groupe de maladies génétiques multi-systémiques liées à un dysfonctionnement du cil primaire, une structure sensorielle présente à la surface des cellules qui régule des voies de signalisation clés au cours du développement et de l'homéostasie tissulaire. Afin d'identifier de nouveaux gènes responsables de ciliopathies développementales sévères, ~ 500 patients / fétus ont été analysés par une approche de séquençage à haut débit de l'exome ciblant > 1 200 gènes ciliaires ("ciliome"). Nous avons identifié huit nouvelles mutations dans le gène NEK8/NPHP9 chez cinq familles dont les syndromes se chevauchent. NEK8/NPHP9 code une protéine kinase de la famille des NIMA qui se localise au niveau du compartiment Inversine du cil primaire et agit comme un régulateur de la signalisation
Hippo, une voie essentielle contrôlant la taille des organes. Nous montrons pour la première fois que les mutations du gène NEK8 sont associées à une agénésie rénale et une hypodysplasie. De plus, notre travail met en évidence une corrélation génotype/phénotype: les mutations "perte de fonction" de NEK8 conduisant à reins élargies et kystiques, des kystes pancréatiques et hépatique, alors que les mutations faux-sens de NEK8 causent une hypodysplasie/agénésie rénale associée à une cardiopathie et une paucité des canaux biliaires. La première partie de mon projet de thèse porte sur l'étude de l'impact des mutations faux-sens de NEK8 sur divers processus cellulaires et des voies de signalisation dépendantes de NEK8. Nous avons démontré un effet "gain de fonction" des mutations faux-sens de NEK8 puisqu'elles affectent la ciliogenèse et la composition du compartiment Inversine (localisation ciliaire de ANKS6). De plus, ces mutations altèrent la localisation nucléaire de YAP, le principal acteur de la voie
Hippo, ainsi que l'expression des gènes cibles de YAP dans les fibroblastes de patients et dans la lignée cellulaire rénale (mIMCD3) invalidée pour NEK8. De même, nous avons montré une accumulation anormale de YAP nucléaire dans les reins polykystiques de la souris Jck, porteuse d'une mutation faux-sens de Nek8. Un déséquilibre de la voie
Hippo serait donc à l'origine des défauts de morphogenèses épithéliales. En effet, les cellules mIMCD3 invalidées pour NEK8 forment en culture 3D des structures anormales et/ou des sphères élargies qui s'accompagnent d'une persistance du marquage nucléaire de YAP et Ki-67 et forment de grandes sphères par rapport aux cellules contrôles. Des défauts plus sévères ont été observés pour les cellules ré-exprimant les différents mutants de NEK8, confirmant la pathogénicité de ces mutations et leur effet "gain de fonction". Enfin, le traitement par la Vertéporfine, un inhibiteur spécifique de l'activité transcriptionnelle de YAP, améliore non seulement le phénotype des fibroblastes de patients et des cellules rénales invalidées pour NEK8 en culture 3D, mais également in vivo les anomalies observées chez les embryons de poisson zèbre dues à la surexpression de la forme NEK8 humaine, confirmant…
Advisors/Committee Members: Saunier, Sophie (thesis director).
Subjects/Keywords: NEK8/NPHP9; Cil primaire; Ciliopathies rénales; Voie de signalisation de Hippo; NEK8/NPHP9; Primary cilium; Renal ciliopathies; Hippo pathway; 571.96
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Grampa, V. (2015). Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2015USPCB099
Chicago Manual of Style (16th Edition):
Grampa, Valentina. “Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères.” 2015. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021.
http://www.theses.fr/2015USPCB099.
MLA Handbook (7th Edition):
Grampa, Valentina. “Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères.” 2015. Web. 19 Jan 2021.
Vancouver:
Grampa V. Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2015. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2015USPCB099.
Council of Science Editors:
Grampa V. Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies : Caractérisation des mécanismes physiopathologiques associés aux mutations NEK8 / NPHP9 identifiées chez des patients atteints de ciliopathies rénales sévères. [Doctoral Dissertation]. Sorbonne Paris Cité; 2015. Available from: http://www.theses.fr/2015USPCB099
26.
Sabra, Hiba.
Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1.
Degree: Docteur es, Biologie du développement - Oncogenèse, 2017, Grenoble Alpes
URL: http://www.theses.fr/2017GREAV026
► L'adhérence cellulaire à la matrice extracellulaire joue un rôle clé dans leur prolifération,leur différenciation ou l'apoptose. Par conséquent ce processus est critique pour undéveloppement normal…
(more)
▼ L'adhérence cellulaire à la matrice extracellulaire joue un rôle clé dans leur prolifération,leur différenciation ou l'apoptose. Par conséquent ce processus est critique pour undéveloppement normal et pour l'homéostasie tissulaire. La dérégulation de ce mécanismecontribue souvent à des situations pathologiques. Ainsi, la dérégulation de nombreux gènesimpliqués dans les adhérences cellule-cellule ou cellule-matrice extracellulaire sont liés à despathologies conduisant à un défaut de développement, la progression tumorale, oul'inflammation.Les intégrines sont des récepteurs transmembranaires hétéro dimériques jouant un rôlemajeur dans les interactions cellule-matrice extracellulaire. Ce rôle n'est pas limité à unesimple interaction mécanique puisqu'elles permettent également la transduction dessignaux de la matrice extracellulaire à la cellule afin de permettre à cette dernière des'adapter à son micro environnement. Dans le but d’étudier le rôle des intégrines à chaîneβ1 dans le développement osseux, le laboratoire a mis en place un modèle murind'inactivation conditionnelle du gène Itgb1 basée sur l'expression de la recombinase Cre austade pré-ostéoblastique. Les souris mutées présentent un défaut de développementosseux, dû à une faible prolifération des ostéoblastes.Contrairement à ce qui était généralement admis, cette faible prolifération desostéoblastes est indépendante de la voie classique mettant en jeu la voie classique des MAPkinases. En revanche, elle est contrôlée par la voie Hippo: cette signalisation a étérécemment identifiée chez la Drosophile et les Mammifères comme un mécanismeinhibiteur majeur de la prolifération cellulaire. Le cofacteur de transcription YAP, effecteurfinal de cette voie, est une navette nucléo-cytoplasmique. Son expression est amplifiée dansdivers cancers dont l'ostéosarcome où cette surexpression associée à celle de l’Itgb1 est unfacteur de mauvais pronostique.Mes travaux consistent à comprendre comment les intégrines à chaîne β1 contrôlent lavoie Hippo, et donc la prolifération. Nous avons confirmé que la délétion des intégrines β16active la phosphorylation de YAP et sa séquestration dans le cytoplasme. En utilisant destechniques de Biologie Cellulaire et de Biochimie, nous avons montré que suite à la délétionde l’Itgb1, les cellules présentent un défaut de trafic vésiculaire réduisant la translocationmembranaire de Rac1. La séquestration cytoplasmique de Rac1 diminue l’activation de soneffecteur majeur la kinase PAK responsable de la dissociation d'un complexe membranaired'inactivation composé de la protéine adaptatrice NF2, la kinase LATS et de son effecteurprincipal YAP. Les intégrines en provocant la perte de ce complexe induisent ladéphosphorylation de YAP, sa translocation nucléaire et donc stimulent la proliférationcellulaire.
Cell adhesion to the extracellular matrix plays a key role in their proliferation,differentiation or apoptosis. Therefore, this process is critical for normal development andtissue homeostasis. The deregulation of this mechanism often contributes to…
Advisors/Committee Members: Bouvard, Daniel (thesis director).
Subjects/Keywords: Intégrines beta 1; Voie Hippo; Trafic vésiculaire; Rac1; Pak; Beta 1 integrins; Hippo pathway; Vesicular traffic; Rac1; Pak; 570
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sabra, H. (2017). Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1. (Doctoral Dissertation). Grenoble Alpes. Retrieved from http://www.theses.fr/2017GREAV026
Chicago Manual of Style (16th Edition):
Sabra, Hiba. “Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1.” 2017. Doctoral Dissertation, Grenoble Alpes. Accessed January 19, 2021.
http://www.theses.fr/2017GREAV026.
MLA Handbook (7th Edition):
Sabra, Hiba. “Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1.” 2017. Web. 19 Jan 2021.
Vancouver:
Sabra H. Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1. [Internet] [Doctoral dissertation]. Grenoble Alpes; 2017. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2017GREAV026.
Council of Science Editors:
Sabra H. Etude des mécanismes moléculaires régulant la voie Hippo via les intégrines ß1 : Study of the molecular mechanisms regulating the Hippo pathway via the integrins b1. [Doctoral Dissertation]. Grenoble Alpes; 2017. Available from: http://www.theses.fr/2017GREAV026
Université Paris-Sud – Paris XI
27.
Cabochette, Pauline.
CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS.
Degree: Docteur es, Biologie, 2014, Université Paris-Sud – Paris XI
URL: http://www.theses.fr/2014PA11T089
► Contrairement aux mammifères adultes, la rétine des amphibiens possède la particularité de croître durant toute la vie de l'animal grâce à l'activité continue d'une population…
(more)
▼ Contrairement aux mammifères adultes, la rétine des amphibiens possède la particularité de croître durant toute la vie de l'animal grâce à l'activité continue d'une population de cellules souches localisée au sein d'une niche bien délimitée, la zone marginale ciliaire (ZMC). Ce modèle offre ainsi la possibilité d'étudier in vivo les mécanismes moléculaires à l'origine du maintien et de la prolifération des cellules souches neurales à des stades post-embryonnaires. Dans ce but, l'identification et la caractérisation des différentes voies de signalisation présentes au sein de la niche biologique des cellules souches rétiniennes est une première étape indispensable. Mon projet de thèse a été divisé en deux objectifs principaux: l'étude des interactions entre les voies Wnt et Hedgehog au sein de la ZMC chez le xénope et la réalisation de l'étude fonctionnelle de Yap, l'effecteur principal de la voie de signalisation Hippo dans ce modèle. Par des approches génétiques et pharmacologiques, la première partie de ce projet a permis de mettre en évidence un antagonisme inattendu entre les signaux Wnt et Hedgehog au sein de la ZMC qui régule l'activité proliférative des cellules souches et des progéniteurs rétiniens. Ce travail nous a conduit à proposer un modèle dans lequel ces deux voies réguleraient la balance prolifération/différenciation dans la rétine post-embryonnaire. Dans un deuxième temps, les expériences de gain et de perte de fonction du gène Yap ont montré que ce dernier joue un rôle essentiel dans la régulation du programme temporel de la phase de réplication de l'ADN des cellules souches rétiniennes. En effet, l'inhibition de Yap entraîne une importante réduction de la durée de la phase S du cycle cellulaire associée à une instabilité génomique. Une surexpression de c-Myc et de la voie p53-p21 semble impliquée dans ce phénotype. Nos travaux nous ont également permis d'identifier un nouveau partenaire de YAP, le facteur de transcription PKNOX1. L'ensemble de ces données nous a ainsi conduit à proposer un modèle selon lequel le complexe YAP/PKNOX1 pourrait être nécessaire au bon déroulement de la phase de réplication des cellules souches, indispensable à la maintenance de l'intégrité du génome de ces cellules et de leur descendance.
In contrast to the adult mammals, the retina of amphibians shows continuous growth during adulthood through active neural stem cells localized in the defined niche called ciliary marginal zone (CMZ). This model offers an exceptional tool to study in vivo the molecular mechanisms involved in the maintenance and proliferation of neural stem cells during post-embryonic stages. In this order, the identification and the characterization of the signaling pathways acting in biological retinal stem cell niche is an essential step.My PhD research was divided in two main parts: the study of the interaction between the Wnt and Hedgehog pathways within the CMZ and the functional study of Yap, the downstream effector of the Hippo pathway in this model. By using genetic and pharmacological tools,…
Advisors/Committee Members: Perron, Muriel (thesis director), Bronchain, Odile (thesis director).
Subjects/Keywords: Cellules souches; Retine; Yap; Hippo; Wnt; Hedgehog; Xénope; Stem cells; Retina; Yap; Hippo; Wnt; Hedgehog; Xenopus
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cabochette, P. (2014). CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2014PA11T089
Chicago Manual of Style (16th Edition):
Cabochette, Pauline. “CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS.” 2014. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed January 19, 2021.
http://www.theses.fr/2014PA11T089.
MLA Handbook (7th Edition):
Cabochette, Pauline. “CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS.” 2014. Web. 19 Jan 2021.
Vancouver:
Cabochette P. CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2014. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2014PA11T089.
Council of Science Editors:
Cabochette P. CARACTERISATION DU RESEAU DE SIGNALISATION IMPLIQUE DANS LA MAINTENANCE ET LA PROLIFERATION DES CELLULES SOUCHES DE LA RETINE DU XENOPE : CHARACTERIZATION OF THE SIGNALING NETWORK INVOLVED IN THE MAINTENANCE AND PROLIFERATION OF XENOPUS RETINAL STEM CELLS. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2014. Available from: http://www.theses.fr/2014PA11T089
University of Washington
28.
Sczaniecka, Anna.
The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway.
Degree: PhD, 2015, University of Washington
URL: http://hdl.handle.net/1773/33210
► The Hippo signal transduction pathway plays a pivotal role in regulation of normal development, adult organ homeostasis, and cancer. At the core of the Hippo…
(more)
▼ The
Hippo signal transduction pathway plays a pivotal role in regulation of normal development, adult organ homeostasis, and cancer. At the core of the
Hippo pathway, MST1/2 kinases phosphorylate and activate LATS1/2 kinases, which in turn phosphorylate and inactivate transcriptional co-activators YAP1 and TAZ. Phosphorylated YAP1 and TAZ are inhibited from entering the nucleus and are instead cytoplasmically retained or degraded. Cells monitor their microenvironment, by sensing local cell density and cellular polarity, and use
Hippo signaling to regulate the maintenance of normal cell numbers necessary for tissue function. The mechanisms responsible for the connection between the cellular microenvironment and
Hippo pathway are poorly understood. In this study, in collaboration with Dr. Andrew Emili's laboratory in the University of Toronto, I reveal a novel mechanistic connection between the
Hippo signaling pathway and the apical-basal cell polarity protein DLG5. I found that DLG5 binds to MST1/2 kinases of the core
Hippo pathway. Inactivation of Dlg5 in mice in vivo and in primary cells ex vivo results in increased
Hippo pathway activity and decreased levels and activity of YAP1 and TAZ. Overexpression of DLG5 inhibits
Hippo signaling and promotes the expression of
Hippo pathway target genes. In genetic epistasis experiments in mice, Dlg5 shows a strong genetic interaction with both Yap1 and Taz (Wwtr1). Mechanistically, I found that DLG5 negatively regulates the
Hippo pathway by inhibiting the binding between MST1/2 and LATS1/2. This study increases the understanding of the connection between apical-basal polarity and the
Hippo pathway and identifies apical-basal polarity family protein DLG5 as a novel interactor and regulator of the
Hippo signal transduction pathway.
Advisors/Committee Members: Vasioukhin, Valeri I (advisor).
Subjects/Keywords: Apical-Basal Polarity; DLG5; Hippo; Hippo Pathway; LATS; MST; Molecular biology; Cellular biology; molecular and cellular biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sczaniecka, A. (2015). The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/33210
Chicago Manual of Style (16th Edition):
Sczaniecka, Anna. “The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway.” 2015. Doctoral Dissertation, University of Washington. Accessed January 19, 2021.
http://hdl.handle.net/1773/33210.
MLA Handbook (7th Edition):
Sczaniecka, Anna. “The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway.” 2015. Web. 19 Jan 2021.
Vancouver:
Sczaniecka A. The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway. [Internet] [Doctoral dissertation]. University of Washington; 2015. [cited 2021 Jan 19].
Available from: http://hdl.handle.net/1773/33210.
Council of Science Editors:
Sczaniecka A. The Role and Mechanisms of Dlg5 in the Regulation of the Hippo Signaling Pathway. [Doctoral Dissertation]. University of Washington; 2015. Available from: http://hdl.handle.net/1773/33210
29.
Loudhaief, Rihab.
Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology.
Degree: Docteur es, Sciences de la vie, 2016, Université Côte d'Azur (ComUE)
URL: http://www.theses.fr/2016AZUR4054
► Le tube digestif est la première barrière contre les agresseurs présents dans la nourriture (virus, bactéries, produits chimiques, pesticides etc...). Il doit donc maintenir au…
(more)
▼ Le tube digestif est la première barrière contre les agresseurs présents dans la nourriture (virus, bactéries, produits chimiques, pesticides etc...). Il doit donc maintenir au mieux son intégrité structurale et fonctionnelle tout au long de la vie de l'individu. Bien que l'impact délétère d'une intoxication aiguë puisse être surmonté par la capacité de défense et de régénération de la muqueuse digestive, une agression prolongée ou répétée peut compromettre l'équilibre physiologique (l'homéostasie) du tube digestif. Parmi les agresseurs pouvant être ingérés avec la nourriture, on trouve la bactérie Bacillus thuringiensis (Bt) et représente 70% des ventes de bioinsecticides. Bt est une bactérie Gram+ sporulante qui produit, pendant la sporulation, des toxines nommées Cry. Parmi les différentes souches de Bt, certaines ont été sélectionnées pour la spécificité d'action de leurs toxines Cry contre des nuisibles et sont commercialisées sous forme de sporanges. Certaines de ces souches sont utilisées en agriculture biologique en France et l'accroissement de leur utilisation fait qu'elles sont de plus en plus présentes dans la nourriture, source de contamination potentielle pour l'homme et l’environnement. La question qui se pose maintenant est de savoir si un tel accroissement de l’utilisation de Bt peut avoir des impacts sur des espèces non cibles. Mon projet de thèse a consisté en l’étude des conséquences de l'ingestion de Bt (sous forme végétative ou de sporanges) sur la physiologie intestinale de la drosophile (animal non sensible à Bt en termes de toxicité aigüe
The digestive tract is continuously subjected to multiple aggressions through virus, bacteria, toxins and chemicals mixed in the feed. Therefore the gut lining has established a mechanism of replenishment in order to maintain the physiological function of the organ called the gut homeostasis. Although the deleterious impact of acute poisoning can be overcome by the defense capacity and regeneration of the gut mucosa, prolonged or repeated intoxication can impair its homeostasis. Among the aggressors hidden in the feed, there is the bacterium Bacillus thuringiensis (Bt). Bt is worldwide used as bioinsecticide. Indeed the multitude of Bt strains produces a broad range of crystalline toxins, named Cry toxins, which certain have been selected in organic farming owing to their lethal properties against specific pests. Because of incentive programs for sustainable development, the use of Bt bioinsecticides as an alternative to chemical pesticides will further increase in the next decades. Although the specificity of the acute toxicity of Cry toxins has been proved since many years, data are scarce on adverse effects that could result from chronic exposure. The question now is how far non-target organisms will be potentially impacted by the resulting augmentation of the Bt bacterium and its Cry toxins in the environment. To answer this challenge, I used Drosophila (a non-target organism) to study the impacts of Bt bioinsecticides on the gut physiology because 1/…
Advisors/Committee Members: Gallet, Armel (thesis director).
Subjects/Keywords: Bacillus thuringiensis; Physiologie intestinale; JNK; Hippo; Bactéries opportunistes; Bacillus thuringiensis; Intestinal physiology; JNK; Hippo; Opportunistic bacteria
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Loudhaief, R. (2016). Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology. (Doctoral Dissertation). Université Côte d'Azur (ComUE). Retrieved from http://www.theses.fr/2016AZUR4054
Chicago Manual of Style (16th Edition):
Loudhaief, Rihab. “Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology.” 2016. Doctoral Dissertation, Université Côte d'Azur (ComUE). Accessed January 19, 2021.
http://www.theses.fr/2016AZUR4054.
MLA Handbook (7th Edition):
Loudhaief, Rihab. “Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology.” 2016. Web. 19 Jan 2021.
Vancouver:
Loudhaief R. Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology. [Internet] [Doctoral dissertation]. Université Côte d'Azur (ComUE); 2016. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2016AZUR4054.
Council of Science Editors:
Loudhaief R. Effets des bioinsecticides à base de Bacillus thuringiensis sur la physiologie intestinale de la Drosophile : Effects of Bacillus thuringiensis bioinsecticides on the Drosophila gut physiology. [Doctoral Dissertation]. Université Côte d'Azur (ComUE); 2016. Available from: http://www.theses.fr/2016AZUR4054
30.
Meléndez García, Rodrigo.
YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2020, université Paris-Saclay
URL: http://www.theses.fr/2020UPASL014
► Une cellule souche est capable de s’auto-renouveler et de générer des cellules différenciées après division cellulaire. La duplication complète de son génome doit être exempte…
(more)
▼ Une cellule souche est capable de s’auto-renouveler et de générer des cellules différenciées après division cellulaire. La duplication complète de son génome doit être exempte d'erreurs afin d'éviter la propagation aux cellules filles de mutations délétères. Chez les eucaryotes, il a été montré que des segments d’ADN sur les chromosomes se répliquent de manière coordonnée et à des moments définis pendant la phase de synthèse, un processus appelé programme spatio-temporel de réplication de l'ADN (RT). Des changements majeurs dans le RT sont corrélés avec les changements de détermination des cellules souches et associés à l'organisation et à l’expressivité du génome. Malgré ce rôle central, les mécanismes qui sous-tendent le contrôle du RT restent méconnus. Mon laboratoire a mis en évidence que YAP, l'effecteur en aval de la voie de signalisation Hippo impliquée dans la croissance cellulaire, régule la vitesse et la chorégraphie de la réplication de l’ADN des cellules souches rétiniennes chez l’amphibien xénope. Ces données révèlent YAP comme un nouvel acteur moléculaire dans le contrôle du RT. Pour tester l’implication directe de YAP dans la dynamique de réplication de l’ADN, nous avons tiré profit du système in vitro d’extraits d'œufs de xénope dans lequel toutes les étapes du processus sont reproduites de manière synchrone. Nous montrons que YAP est recruté à la chromatine pendant la réplication et que ce processus se produit seulement après la phase d’initiation des origines de réplication. Des extraits déplétés de la protéine YAP présentent une accélération de la vitesse de réplication et une augmentation du nombre de sites d’activation de la synthèse de l’ADN. Par ailleurs, nous avons identifié RIF1 (Rap1-Interacting Factor 1 ou Replication Timing Regulatory Factor 1), un des rares régulateurs connus du RT, comme un nouveau partenaire de YAP. Comme pour YAP, la perte de fonction de RIF1 dans les embryons de xénope conduit à un phénotype de petit œil et à la dérégulation du RT dans les cellules souches rétiniennes.Dans l'ensemble, nos résultats montrent l’implication de YAP dans le contrôle de la dynamique de réplication de l’ADN et révèlent RIF1 comme un nouveau partenaire dans ce processus. Ce travail ouvre de nouvelles perspectives d’étude quant à l’importance biologique de cette interaction YAP-RIF1 dans le contrôle du RT et sa pertinence comme cible pour influencer le devenir des cellules souches.
Stemness could be defined as a state in which a cell is able to self-renew and/or to differentiate after cell division. Before this happens, exhaustive duplication of the genome free of errors must occur in order to avoid deleterious mutations, a hallmark of cancer. Thus, DNA replication is particularly important to stem cells because of their continuous division capacities. Regarding DNA replication in eukaryotes, it was discovered that segments of chromosomes close in space, replicate in a coordinated manner during S phase, a process called replication timing. Moreover, major changes in replication timing…
Advisors/Committee Members: Perron, Muriel (thesis director), Bronchain, Odile (thesis director).
Subjects/Keywords: Réplication de l'ADN; Cellules souches; Voie de signalisation Hippo/YAP; DNA replication; Stem cells; Hippo/YAP signaling pathway
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Meléndez García, R. (2020). YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN. (Doctoral Dissertation). université Paris-Saclay. Retrieved from http://www.theses.fr/2020UPASL014
Chicago Manual of Style (16th Edition):
Meléndez García, Rodrigo. “YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN.” 2020. Doctoral Dissertation, université Paris-Saclay. Accessed January 19, 2021.
http://www.theses.fr/2020UPASL014.
MLA Handbook (7th Edition):
Meléndez García, Rodrigo. “YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN.” 2020. Web. 19 Jan 2021.
Vancouver:
Meléndez García R. YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN. [Internet] [Doctoral dissertation]. université Paris-Saclay; 2020. [cited 2021 Jan 19].
Available from: http://www.theses.fr/2020UPASL014.
Council of Science Editors:
Meléndez García R. YAP as a Regulator of DNA Replication Timing : YAP comme régulateur du programme de réplication de l'ADN. [Doctoral Dissertation]. université Paris-Saclay; 2020. Available from: http://www.theses.fr/2020UPASL014
◁ [1] [2] [3] [4] [5] [6] [7] [8] ▶
. 
Open Access Theses and Dissertations
