Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2.
Nat Cell Biol
; 9(3): 331-8, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17293853
ABSTRACT
The p300-CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) involved in the reversible acetylation of various transcriptional regulators, including the tumour suppressor p53. It is implicated in many cellular processes, such as transcription, differentiation, proliferation and apoptosis. We observed that knockdown of PCAF expression in HeLa or U2OS cell lines induces stabilization of the oncoprotein Hdm2, a RING finger E3 ligase primarily known for its role in controlling p53 stability. To investigate the molecular basis of this effect, we examined whether PCAF is involved in Hdm2 ubiquitination. Here, we show that PCAF, in addition to its acetyltransferase activity, possesses an intrinsic ubiquitination activity that is critical for controlling Hdm2 expression levels, and thus p53 functions. Our data highlight a regulatory crosstalk between PCAF and Hdm2 activities, which is likely to have a central role in the subtle control of p53 activity after DNA damage.
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Bases de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Ciclo Celular
/
Ubiquitina-Proteína Ligases
/
Proteínas Proto-Oncogênicas c-mdm2
/
Histona Acetiltransferases
Limite:
Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França