Role of p27Kip1 as a transcriptional regulator

The protein p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors. It interacts with both the catalytic and the regulatory subunit (cyclin) and introduces a region into the catalytic cleave of the Cdk inducing its inactivation. Its inhibitory capacity can be modulated...

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Autores: Bachs Valldeneu, Oriol, Gallastegui Calvache, Edurne, Orlando, Serena, Bigas Salvans, Anna, Morante-Redolat, José Manuel, Serratosa, Joan, Fariñas, Isabel, Aligué, Rosa, Pujol Sobrevía, María Jesús
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/41926
Acceso en línea:http://hdl.handle.net/10230/41926
http://dx.doi.org/10.18632/oncotarget.25447
Access Level:acceso abierto
Palabra clave:Cancer
Neurodegeneration
p27Kip1
Transcriptional regulation
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spelling Role of p27Kip1 as a transcriptional regulatorBachs Valldeneu, OriolGallastegui Calvache, EdurneOrlando, SerenaBigas Salvans, AnnaMorante-Redolat, José ManuelSerratosa, JoanFariñas, IsabelAligué, RosaPujol Sobrevía, María JesúsCancerNeurodegenerationp27Kip1Transcriptional regulationThe protein p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors. It interacts with both the catalytic and the regulatory subunit (cyclin) and introduces a region into the catalytic cleave of the Cdk inducing its inactivation. Its inhibitory capacity can be modulated by specific tyrosine phosphorylations. p27Kip1 also behaves as a transcriptional regulator. It associates with specific chromatin domains through different transcription factors. ChIP on chip, ChIP-seq and expression microarray analysis allowed the identification of the transcriptional programs regulated by p27Kip1. Thus, important cellular functions as cell division cycle, respiration, RNA processing, translation and cell adhesion, are under p27Kip1 regulation. Moreover, genes involved in pathologies as cancer and neurodegeneration are also regulated by p27Kip1, suggesting its implication in these pathologies. The carboxyl moiety of p27Kip1 can associate with different proteins, including transcriptional regulators. In contrast, its NH2-terminal region specifically interacts with cyclin-Cdk complexes. The general mechanistic model of how p27Kip1 regulates transcription is that it associates by its COOH region to the transcriptional regulators on the chromatin and by the NH2-domain to cyclin-Cdk complexes. After Cdk activation it would phosphorylate the specific targets on the chromatin leading to gene expression. This model has been demonstrated to apply in the transcriptional regulation of p130/E2F4 repressed genes involved in cell cycle progression. We summarize in this review our current knowledge on the role of p27Kip1 in the regulation of transcription, on the transcriptional programs under its regulation and on its relevance in pathologies as cancer and neurodegeneration.Impact Journal201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/41926http://dx.doi.org/10.18632/oncotarget.25447reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCopyright : © 2018 Bachs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedhttps://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/419262026-05-29T05:05:01Z
dc.title.none.fl_str_mv Role of p27Kip1 as a transcriptional regulator
title Role of p27Kip1 as a transcriptional regulator
spellingShingle Role of p27Kip1 as a transcriptional regulator
Bachs Valldeneu, Oriol
Cancer
Neurodegeneration
p27Kip1
Transcriptional regulation
title_short Role of p27Kip1 as a transcriptional regulator
title_full Role of p27Kip1 as a transcriptional regulator
title_fullStr Role of p27Kip1 as a transcriptional regulator
title_full_unstemmed Role of p27Kip1 as a transcriptional regulator
title_sort Role of p27Kip1 as a transcriptional regulator
dc.creator.none.fl_str_mv Bachs Valldeneu, Oriol
Gallastegui Calvache, Edurne
Orlando, Serena
Bigas Salvans, Anna
Morante-Redolat, José Manuel
Serratosa, Joan
Fariñas, Isabel
Aligué, Rosa
Pujol Sobrevía, María Jesús
author Bachs Valldeneu, Oriol
author_facet Bachs Valldeneu, Oriol
Gallastegui Calvache, Edurne
Orlando, Serena
Bigas Salvans, Anna
Morante-Redolat, José Manuel
Serratosa, Joan
Fariñas, Isabel
Aligué, Rosa
Pujol Sobrevía, María Jesús
author_role author
author2 Gallastegui Calvache, Edurne
Orlando, Serena
Bigas Salvans, Anna
Morante-Redolat, José Manuel
Serratosa, Joan
Fariñas, Isabel
Aligué, Rosa
Pujol Sobrevía, María Jesús
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Neurodegeneration
p27Kip1
Transcriptional regulation
topic Cancer
Neurodegeneration
p27Kip1
Transcriptional regulation
description The protein p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors. It interacts with both the catalytic and the regulatory subunit (cyclin) and introduces a region into the catalytic cleave of the Cdk inducing its inactivation. Its inhibitory capacity can be modulated by specific tyrosine phosphorylations. p27Kip1 also behaves as a transcriptional regulator. It associates with specific chromatin domains through different transcription factors. ChIP on chip, ChIP-seq and expression microarray analysis allowed the identification of the transcriptional programs regulated by p27Kip1. Thus, important cellular functions as cell division cycle, respiration, RNA processing, translation and cell adhesion, are under p27Kip1 regulation. Moreover, genes involved in pathologies as cancer and neurodegeneration are also regulated by p27Kip1, suggesting its implication in these pathologies. The carboxyl moiety of p27Kip1 can associate with different proteins, including transcriptional regulators. In contrast, its NH2-terminal region specifically interacts with cyclin-Cdk complexes. The general mechanistic model of how p27Kip1 regulates transcription is that it associates by its COOH region to the transcriptional regulators on the chromatin and by the NH2-domain to cyclin-Cdk complexes. After Cdk activation it would phosphorylate the specific targets on the chromatin leading to gene expression. This model has been demonstrated to apply in the transcriptional regulation of p130/E2F4 repressed genes involved in cell cycle progression. We summarize in this review our current knowledge on the role of p27Kip1 in the regulation of transcription, on the transcriptional programs under its regulation and on its relevance in pathologies as cancer and neurodegeneration.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/41926
http://dx.doi.org/10.18632/oncotarget.25447
url http://hdl.handle.net/10230/41926
http://dx.doi.org/10.18632/oncotarget.25447
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journal
publisher.none.fl_str_mv Impact Journal
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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