TITLE

p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2

AUTHOR(S)
Ito, Akihiro; Chun-Hsiang Lai; Xuan Zhao; Shin'ichi Saito; Hamilton, Maria H.; Appella, Ettore; Tso-Pang Yao
PUB. DATE
March 2001
SOURCE
EMBO Journal;3/15/2001, Vol. 20 Issue 6, p1331
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The tumor suppressor p53 is activated in response to many types of cellular and environmental insults via mechanisms involving post-translational modification. Here we demonstrate that, unlike phosphorylation, p53 invariably undergoes acetylation in cells exposed to a variety of stress-inducing agents including hypoxia, anti-metabolites, nuclear export inhibitor and actinomycin D treatment. In vivo, p53 acetylation is mediated by the p300 and CBP acetyltransferases. Overexpression of either p300 or CBP, but not an acetyltransferase-deficient mutant, efficiently induces specific p53 acetylation. In contrast, MDM2, a negative regulator of p53, actively suppresses p300/CBP-mediated p53 acetylation in vivo and in vitro. This inhibitory activity of MDM2 on p53 acetylation is in turn abrogated by tumor suppressor p19ARF, indicating that regulation of acetylation is a central target of the p53-MDM2-p19ARF feedback loop. Functionally, inhibition of deacetylation promotes p53 stability, suggesting that acetylation plays a positive role in the accumulation of p53 protein in stress response. Our results provide evidence that p300/CBP-mediated acetylation may be a universal and critical modifi cation for p53 function.
ACCESSION #
12954973

 

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