The role of TCTEX1D4/PPP1 complex in cell proliferation and migration
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/12507 |
Resumo: | Prostate cancer is one of the most prevalent and incident cancer in men, being a disquieting cause of men’s death worldwide. The widespread implementation of prostate-specific antigen (PSA) screening and the improvements on prostate cancer therapy have been leading to a markedly decrease in mortality. However, PSA use is controversial since it has been leading to the diagnosis and treatment of several prostate cancer cases that would not otherwise cause symptoms or threaten man’s life. Hence, the establishment of a panel of biomarkers and the discovery of new therapeutical targets for prostate cancer is a pressing need. Changes in several cell signaling pathways have been associated with de onset, development, and progression of prostate cancer. TGFβ signaling counterbalanced the mitogenic effects of androgens, thus being one of the most prominent pathways involved in controlling prostate growth. Mediators of TGFβ signaling pathway are strictly regulated by several mechanisms, among which reversible phosphorylation. This process involves a fine equilibrium between the action of protein kinases and phosphatases. PPP1 is a major serine/threonine phosphatase that regulates numerous cellular events, including TGFβ signaling. The majority of its functions are accomplished by association with regulatory subunits, known as PPP1-interacting proteins (PIPs). Recently, a novel PIP was found: TCTEX1D4, a dynein light chain protein that was already established as an interactor of TGFβ receptors. Its functions, nevertheless, remain poorly understood. This work identified TCTEX1D4 as an anti-proliferative agent in human prostate cells. Also, TCTEX1D4 activity seems to be regulated through binding to PPP1, as the disruption of TCTEX1D4/PPP1 complex resulted in enhancement of cell proliferation inhibition. Alternatively or in addition, TCTEX1D4 may indirectly regulate PPP1 function by modulating its subcellular localization. This complex doesn´t appear to play a major role in cell migration. Given the results, TCTEX1D4/PPP1 complex may constitute a potential target for the development of new prostate cancer therapies. |
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The role of TCTEX1D4/PPP1 complex in cell proliferation and migrationBiomedicinaCancro da próstataFosforilaçãoProstate cancer is one of the most prevalent and incident cancer in men, being a disquieting cause of men’s death worldwide. The widespread implementation of prostate-specific antigen (PSA) screening and the improvements on prostate cancer therapy have been leading to a markedly decrease in mortality. However, PSA use is controversial since it has been leading to the diagnosis and treatment of several prostate cancer cases that would not otherwise cause symptoms or threaten man’s life. Hence, the establishment of a panel of biomarkers and the discovery of new therapeutical targets for prostate cancer is a pressing need. Changes in several cell signaling pathways have been associated with de onset, development, and progression of prostate cancer. TGFβ signaling counterbalanced the mitogenic effects of androgens, thus being one of the most prominent pathways involved in controlling prostate growth. Mediators of TGFβ signaling pathway are strictly regulated by several mechanisms, among which reversible phosphorylation. This process involves a fine equilibrium between the action of protein kinases and phosphatases. PPP1 is a major serine/threonine phosphatase that regulates numerous cellular events, including TGFβ signaling. The majority of its functions are accomplished by association with regulatory subunits, known as PPP1-interacting proteins (PIPs). Recently, a novel PIP was found: TCTEX1D4, a dynein light chain protein that was already established as an interactor of TGFβ receptors. Its functions, nevertheless, remain poorly understood. This work identified TCTEX1D4 as an anti-proliferative agent in human prostate cells. Also, TCTEX1D4 activity seems to be regulated through binding to PPP1, as the disruption of TCTEX1D4/PPP1 complex resulted in enhancement of cell proliferation inhibition. Alternatively or in addition, TCTEX1D4 may indirectly regulate PPP1 function by modulating its subcellular localization. This complex doesn´t appear to play a major role in cell migration. Given the results, TCTEX1D4/PPP1 complex may constitute a potential target for the development of new prostate cancer therapies.O cancro da próstata é um dos cancros mais prevalentes e incidentes em homens, sendo uma preocupante causa de morte a nível mundial. A ampla utilização do antigénio específico da próstata (PSA) no seu rastreio e as melhorias na sua terapêutica têm permitido uma diminuição marcada da mortalidade. No entanto, o uso do PSA é controverso uma vez que se verifica um diagnóstico excessivo e o tratamento de vários casos que, eventualmente, não representariam qualquer ameaça para a vida do individuo. Assim, o estabelecimento de novos biomarcadores e a descoberta de novos alvos terapêuticos para o cancro da próstata constitui um importante desafio na atualidade. Alterações em várias vias de sinalização têm sido relacionadas com o desenvolvimento e a progressão do cancro da próstata. A via do TGFβ é uma das vias mais proeminentes no controlo do crescimento da próstata, uma vez que contrabalança os efeitos proliferativos dos androgénios. Um dos principais mecanismos de regulação da via do TGFβ é a fosforilação reversível, executada de modo complementar por proteínas cinases e fosfatases. Uma das fosfatases envolvidas na regulação da via do TGFβ é a PPP1. A PPP1 é uma fosfatase reguladora de inúmeros eventos celulares. A maioria das suas funções envolve a sua ligação a subunidades reguladoras conhecidas como PIPs. Recentemente, foi descrita uma nova PIP, a TCTEX1D4, que já havia sido referida como interactor dos recetores da via do TGFβ. No entanto, pouco se sabe acerca da sua função. Este trabalho permitiu identificar a TCTEX1D4 como agente inibidor da proliferação em células humanas de próstata. A sua atividade parece ser modulada através da ligação à PPP1, uma vez que a disrupção do complexo TCTEX1D4/PPP1 conduziu a uma maior inibição da proliferação celular. Por outro lado, a TCTEX1D4 pode regular indiretamente a atividade da PPP1 ao modular a sua localização no interior da célula. Este complexo não parece atuar ao nível da migração celular. Tendo em conta os presentes resultados, o complexo TCTEX1D4/PPP1 parece constituir um potencial alvo para o desenvolvimento de novas terapias para o cancro da próstata.Universidade de Aveiro2018-07-20T14:00:46Z2013-07-17T00:00:00Z2013-07-172015-07-17T14:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/12507TID:201581949engFelgueiras, Juliana Carina Cardosoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:22:49Zoai:ria.ua.pt:10773/12507Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:48:40.661748Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
title |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
spellingShingle |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration Felgueiras, Juliana Carina Cardoso Biomedicina Cancro da próstata Fosforilação |
title_short |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
title_full |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
title_fullStr |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
title_full_unstemmed |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
title_sort |
The role of TCTEX1D4/PPP1 complex in cell proliferation and migration |
author |
Felgueiras, Juliana Carina Cardoso |
author_facet |
Felgueiras, Juliana Carina Cardoso |
author_role |
author |
dc.contributor.author.fl_str_mv |
Felgueiras, Juliana Carina Cardoso |
dc.subject.por.fl_str_mv |
Biomedicina Cancro da próstata Fosforilação |
topic |
Biomedicina Cancro da próstata Fosforilação |
description |
Prostate cancer is one of the most prevalent and incident cancer in men, being a disquieting cause of men’s death worldwide. The widespread implementation of prostate-specific antigen (PSA) screening and the improvements on prostate cancer therapy have been leading to a markedly decrease in mortality. However, PSA use is controversial since it has been leading to the diagnosis and treatment of several prostate cancer cases that would not otherwise cause symptoms or threaten man’s life. Hence, the establishment of a panel of biomarkers and the discovery of new therapeutical targets for prostate cancer is a pressing need. Changes in several cell signaling pathways have been associated with de onset, development, and progression of prostate cancer. TGFβ signaling counterbalanced the mitogenic effects of androgens, thus being one of the most prominent pathways involved in controlling prostate growth. Mediators of TGFβ signaling pathway are strictly regulated by several mechanisms, among which reversible phosphorylation. This process involves a fine equilibrium between the action of protein kinases and phosphatases. PPP1 is a major serine/threonine phosphatase that regulates numerous cellular events, including TGFβ signaling. The majority of its functions are accomplished by association with regulatory subunits, known as PPP1-interacting proteins (PIPs). Recently, a novel PIP was found: TCTEX1D4, a dynein light chain protein that was already established as an interactor of TGFβ receptors. Its functions, nevertheless, remain poorly understood. This work identified TCTEX1D4 as an anti-proliferative agent in human prostate cells. Also, TCTEX1D4 activity seems to be regulated through binding to PPP1, as the disruption of TCTEX1D4/PPP1 complex resulted in enhancement of cell proliferation inhibition. Alternatively or in addition, TCTEX1D4 may indirectly regulate PPP1 function by modulating its subcellular localization. This complex doesn´t appear to play a major role in cell migration. Given the results, TCTEX1D4/PPP1 complex may constitute a potential target for the development of new prostate cancer therapies. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-07-17T00:00:00Z 2013-07-17 2015-07-17T14:00:00Z 2018-07-20T14:00:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/12507 TID:201581949 |
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http://hdl.handle.net/10773/12507 |
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TID:201581949 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de Aveiro |
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Universidade de Aveiro |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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