Display Settings:

Format

Send to:

Choose Destination
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

Images from this publication.See all images (7)Free text

FIGURE 1.
FIGURE 2.
FIGURE 3.
FIGURE 4.
FIGURE 5.
FIGURE 6.
FIGURE 7.
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