Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/28302
Title: PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27Kip1
Author: Pérez-Luna, Maria
Aguasca i Marsà, Marta
Perearnau, Anna
Serratosa i Serdà, Joan
Martínez Balbás, Marian
Pujol Sobrevía, María Jesús
Bachs Valldeneu, Oriol
Keywords: Inhibidors enzimàtics
Proteïnes quinases
Citologia
Enzyme inhibitors
Protein kinases
Cytology
Issue Date: 29-Apr-2012
Publisher: Oxford University Press
Abstract: 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1093/nar/gks343
It is part of: Nucleic Acids Research, 2012, p. 1-14
Related resource: http://dx.doi.org/10.1093/nar/gks343
URI: http://hdl.handle.net/2445/28302
ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (Biomedicina)

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