Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis

Haim Y. Cohen, Siva Lavu, Kevin J. Bitterman, Brian Hekking, Thomas A. Imahiyerobo, Christine Miller, Roy Frye, Hidde Ploegh, Benedikt M. Kessler, David A. Sinclair

Research output: Contribution to journalArticlepeer-review

502 Scopus citations

Abstract

Apoptosis is a key tumor suppression mechanism that can be initiated by activation of the proapoptotic factor Bax. The Ku70 DNA end-joining protein has recently been shown to suppress apoptosis by sequestering Bax from mitochondria. The mechanism by which Bax is regulated remains unknown. Here, we identify eight lysines in Ku70 that are targets for acetylation in vivo. Five of these, K539, K542, K544, K533, and K556, lie in the C-terminal linker domain of Ku70 adjacent to the Bax interaction domain. We show that CBP and PCAF efficiently acetylate K542 in vitro and associate with Ku70 in vivo. Mimicking acetylation of K539 or K542 or treating cells with deacetylase inhibitors abolishes the ability of Ku70 to suppress Bax-mediated apoptosis. We demonstrate that increased acetylation of Ku70 disrupts the Ku70-Bax interaction and coincides with cytoplasmic accumulation of CBP. These results shed light on the role of acetyltransferases as tumor suppressors.

Original languageEnglish
Pages (from-to)627-638
Number of pages12
JournalMolecular Cell
Volume13
Issue number5
DOIs
StatePublished - 5 Mar 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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