title: PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27 Kip1.
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.
authors.affiliation: Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August-Pi i Sunyer (IDIBAPS), University of Barcelona, 08036-Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pérez-Luna
authors.forename: Marta
authors.initials: M
authors.lastname: Aguasca
authors.forename: Anna
authors.initials: A
authors.lastname: Perearnau
authors.forename: Joan
authors.initials: J
authors.lastname: Serratosa
authors.forename: Marian
authors.initials: M
authors.lastname: Martínez-Balbas
authors.forename: Maria
authors.initials: M
authors.lastname: Jesús Pujol
authors.forename: Oriol
authors.initials: O
authors.lastname: Bachs
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D008239:Lysine; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor