Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2009 Apr 24;284(17):11171-83. doi: 10.1074/jbc.M809268200. Epub 2009 Mar 5.

p53 acetylation is crucial for its transcription-independent proapoptotic functions.

Author information

  • 1Department of Pharmacology and Pennsylvania State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

Abstract

Acetylation of p53 at carboxyl-terminal lysine residues enhances its transcriptional activity associated with cell cycle arrest and apoptosis. Here we demonstrate that p53 acetylation at Lys-320/Lys-373/Lys-382 is also required for its transcription-independent functions in BAX activation, reactive oxygen species production, and apoptosis in response to the histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid and LAQ824. Knock-out of p53 markedly reduced HDACi-induced apoptosis. Unexpectedly, expression of transactivation-deficient p53 variants sensitized p53-null cells to HDACi-mediated BAX-dependent apoptosis, whereas knockdown of endogenous mutant p53 in cancer cells reduced HDACi-mediated cytotoxicity. Evaluation of the mechanisms controlling this response led to the discovery of a novel interaction between p53 and Ku70. The association between these two proteins was acetylation-independent, but acetylation of p53 could prevent and disrupt the Ku70-BAX complex and enhance apoptosis. These results suggest a new mechanism of acetylated p53 transcription-independent regulation of apoptosis.

PMID:
19265193
[PubMed - indexed for MEDLINE]
PMCID:
PMC2670122
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk