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PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1)
P27(Kip1) (p27) is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. Recently, a new function of p27 as transcriptional regulator has been reported. It has been shown that p27 regulates the expression of target genes mostly involved in splicing, cell cycle, respiration and transl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413142/ https://www.ncbi.nlm.nih.gov/pubmed/22547391 http://dx.doi.org/10.1093/nar/gks343 |
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author | Pérez-Luna, Maria Aguasca, Marta Perearnau, Anna Serratosa, Joan Martínez-Balbas, Marian Jesús Pujol, Maria Bachs, Oriol |
author_facet | Pérez-Luna, Maria Aguasca, Marta Perearnau, Anna Serratosa, Joan Martínez-Balbas, Marian Jesús Pujol, Maria Bachs, Oriol |
author_sort | Pérez-Luna, Maria |
collection | PubMed |
description | P27(Kip1) (p27) is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. Recently, a new function of p27 as transcriptional regulator has been reported. It has been shown that p27 regulates the expression of target genes mostly involved in splicing, cell cycle, respiration and translation. We report here that p27 directly binds to the transcriptional coactivator PCAF by a region including amino acids 91–120. PCAF associates with p27 through its catalytic domain and acetylates p27 at lysine 100. Our data showed that overexpression of PCAF induces the degradation of p27 whereas in contrast, the knockdown of PCAF stabilizes the protein. A p27 mutant in which K100 was substituted by arginine (p27-K100R) cannot be acetylated by PCAF and has a half-life much higher than that of p27WT. Moreover, p27-K100R remains stable along cell-cycle progression. Ubiquitylation assays and the use of proteasome inhibitors indicate that PCAF induces p27 degradation via proteasome. We also observed that knockdown of skp2 did not affect the PCAF induced degradation of p27. In conclusion, our data suggest that the p27 acetylation by PCAF regulates its stability. |
format | Online Article Text |
id | pubmed-3413142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34131422012-08-07 PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) Pérez-Luna, Maria Aguasca, Marta Perearnau, Anna Serratosa, Joan Martínez-Balbas, Marian Jesús Pujol, Maria Bachs, Oriol Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics P27(Kip1) (p27) is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. Recently, a new function of p27 as transcriptional regulator has been reported. It has been shown that p27 regulates the expression of target genes mostly involved in splicing, cell cycle, respiration and translation. We report here that p27 directly binds to the transcriptional coactivator PCAF by a region including amino acids 91–120. PCAF associates with p27 through its catalytic domain and acetylates p27 at lysine 100. Our data showed that overexpression of PCAF induces the degradation of p27 whereas in contrast, the knockdown of PCAF stabilizes the protein. A p27 mutant in which K100 was substituted by arginine (p27-K100R) cannot be acetylated by PCAF and has a half-life much higher than that of p27WT. Moreover, p27-K100R remains stable along cell-cycle progression. Ubiquitylation assays and the use of proteasome inhibitors indicate that PCAF induces p27 degradation via proteasome. We also observed that knockdown of skp2 did not affect the PCAF induced degradation of p27. In conclusion, our data suggest that the p27 acetylation by PCAF regulates its stability. Oxford University Press 2012-08 2012-04-30 /pmc/articles/PMC3413142/ /pubmed/22547391 http://dx.doi.org/10.1093/nar/gks343 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Pérez-Luna, Maria Aguasca, Marta Perearnau, Anna Serratosa, Joan Martínez-Balbas, Marian Jesús Pujol, Maria Bachs, Oriol PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title | PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title_full | PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title_fullStr | PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title_full_unstemmed | PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title_short | PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(Kip1) |
title_sort | pcaf regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27(kip1) |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413142/ https://www.ncbi.nlm.nih.gov/pubmed/22547391 http://dx.doi.org/10.1093/nar/gks343 |
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