Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Mol Cell

Publication Date

12/03/2004

Volume

13

Pages

627 - 638

Keywords

Acetylation, Acetyltransferases, Amino Acid Sequence, Animals, Antigens, Nuclear, Apoptosis, Binding Sites, CREB-Binding Protein, Cricetinae, DNA Helicases, DNA-Binding Proteins, Enzyme Inhibitors, HeLa Cells, Histone Acetyltransferases, Humans, Ku Autoantigen, Lysine, Mice, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Sequence Homology, Amino Acid, Trans-Activators, Tumor Suppressor Proteins, bcl-2-Associated X Protein