Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/29047
Title: The transcriptional co-activator PCAF regulates cdk2 activity.
Author: Mateo González, Francesca
Vidal Laliena, Miriam
Canela i Canela, Núria
Zecchin, Annalisa
Martínez Balbás, Marian
Agell i Jané, Neus
Giacca, Mauro
Pujol Sobrevía, María Jesús
Bachs Valldeneu, Oriol
Keywords: Proteïnes quinases
Cicle cel·lular
Citologia
Protein kinases
Cell cycle
Cytology
Issue Date: 22-Sep-2009
Publisher: Oxford University Press
Abstract: Cyclin dependent kinases (cdks) regulate cell cycle progression and transcription. We report here that the transcriptional co-activator PCAF directly interacts with cdk2. This interaction is mainly produced during S and G2/M phases of the cell cycle. As a consequence of this association, PCAF inhibits the activity of cyclin/cdk2 complexes. This effect is specific for cdk2 because PCAF does not inhibit either cyclin D3/cdk6 or cyclin B/cdk1 activities. The inhibition is neither competitive with ATP, nor with the substrate histone H1 suggesting that somehow PCAF disturbs cyclin/cdk2 complexes. We also demonstrate that overexpression of PCAF in the cells inhibits cdk2 activity and arrests cell cycle progression at S and G2/M. This blockade is dependent on cdk2 because it is rescued by the simultaneous overexpression of this kinase. Moreover, we also observed that PCAF acetylates cdk2 at lysine 33. As this lysine is essential for the interaction with ATP, acetylation of this residue inhibits cdk2 activity. Thus, we report here that PCAF inhibits cyclin/cdk2 activity by two different mechanisms: (i) by somehow affecting cyclin/cdk2 interaction and (ii) by acetylating K33 at the catalytic pocket of cdk2. These findings identify a previously unknown mechanism that regulates cdk2 activity.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1093/nar/gkp777
It is part of: Nucleic Acids Research, 2009, vol. 37, num. 21, p. 7072-7084
Related resource: http://dx.doi.org/10.1093/nar/gkp777
URI: http://hdl.handle.net/2445/29047
ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (Biomedicina)

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