Histone deacetylase 3 regulates cyclin a stability

PCAF and GCN5 acetylate cyclin A at specific lysine residues targeting it for degradation at mitosis. We report here that histone deacetylase 3 (HDAC3) directly interacts with and deacetylates cyclin A. HDAC3 interacts with a domain included in the first 171 aa of cyclin A, a region involved in the...

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Detalles Bibliográficos
Autores: Vidal-Laliena, Miriam, Gallastegui, Edurne, Mateo, Francesca, Martínez-Balbás, Marian, Pujol, María Jesús, Bachs, Oriol
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/88197
Acceso en línea:http://hdl.handle.net/10261/88197
Access Level:acceso abierto
Palabra clave:Cell cycle
Cyclins
Protein degradation
Histone deacetylases
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spelling Histone deacetylase 3 regulates cyclin a stabilityVidal-Laliena, MiriamGallastegui, EdurneMateo, FrancescaMartínez-Balbás, MarianPujol, María JesúsBachs, OriolCell cycleCyclinsProtein degradationHistone deacetylasesPCAF and GCN5 acetylate cyclin A at specific lysine residues targeting it for degradation at mitosis. We report here that histone deacetylase 3 (HDAC3) directly interacts with and deacetylates cyclin A. HDAC3 interacts with a domain included in the first 171 aa of cyclin A, a region involved in the regulation of its stability. In cells, overexpression of HDAC3 reduced cyclin A acetylation whereas the knocking down of HDAC3 increased its acetylation. Moreover, reduction of HDAC3 levels induced a decrease of cyclin A that can be reversed by proteasome inhibitors. These results indicate that HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome. Interestingly, HDAC3 is abruptly degraded at mitosis also via proteasome thus facilitating cyclin A acetylation by PCAF/GCN5, which will target cyclin A for degradation. Because cyclin A is crucial for S phase progression and mitosis entry, the knock down of HDAC3 affects cell cycle progression specifically at both, S phase and G2/M transition. In summary we propose here that HDAC3 regulates cyclin A stability by counteracting the action of the acetylases PCAF/GCN5.This work was supported by Grants SAF2009-07769 from the Ministerio de Ciencia e Innovación of Spain and Reticc RD06/0020/0010 from the Istituto de Salud Carlos III.Peer ReviewedAmerican Society for Biochemistry and Molecular BiologyMinisterio de Ciencia e Innovación (España)Instituto de Salud Carlos III2013201320132013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/88197reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1074/jbc.M113.458323info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/881972026-05-22T06:33:51Z
dc.title.none.fl_str_mv Histone deacetylase 3 regulates cyclin a stability
title Histone deacetylase 3 regulates cyclin a stability
spellingShingle Histone deacetylase 3 regulates cyclin a stability
Vidal-Laliena, Miriam
Cell cycle
Cyclins
Protein degradation
Histone deacetylases
title_short Histone deacetylase 3 regulates cyclin a stability
title_full Histone deacetylase 3 regulates cyclin a stability
title_fullStr Histone deacetylase 3 regulates cyclin a stability
title_full_unstemmed Histone deacetylase 3 regulates cyclin a stability
title_sort Histone deacetylase 3 regulates cyclin a stability
dc.creator.none.fl_str_mv Vidal-Laliena, Miriam
Gallastegui, Edurne
Mateo, Francesca
Martínez-Balbás, Marian
Pujol, María Jesús
Bachs, Oriol
author Vidal-Laliena, Miriam
author_facet Vidal-Laliena, Miriam
Gallastegui, Edurne
Mateo, Francesca
Martínez-Balbás, Marian
Pujol, María Jesús
Bachs, Oriol
author_role author
author2 Gallastegui, Edurne
Mateo, Francesca
Martínez-Balbás, Marian
Pujol, María Jesús
Bachs, Oriol
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Cell cycle
Cyclins
Protein degradation
Histone deacetylases
topic Cell cycle
Cyclins
Protein degradation
Histone deacetylases
description PCAF and GCN5 acetylate cyclin A at specific lysine residues targeting it for degradation at mitosis. We report here that histone deacetylase 3 (HDAC3) directly interacts with and deacetylates cyclin A. HDAC3 interacts with a domain included in the first 171 aa of cyclin A, a region involved in the regulation of its stability. In cells, overexpression of HDAC3 reduced cyclin A acetylation whereas the knocking down of HDAC3 increased its acetylation. Moreover, reduction of HDAC3 levels induced a decrease of cyclin A that can be reversed by proteasome inhibitors. These results indicate that HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome. Interestingly, HDAC3 is abruptly degraded at mitosis also via proteasome thus facilitating cyclin A acetylation by PCAF/GCN5, which will target cyclin A for degradation. Because cyclin A is crucial for S phase progression and mitosis entry, the knock down of HDAC3 affects cell cycle progression specifically at both, S phase and G2/M transition. In summary we propose here that HDAC3 regulates cyclin A stability by counteracting the action of the acetylases PCAF/GCN5.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/88197
url http://hdl.handle.net/10261/88197
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1074/jbc.M113.458323
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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