Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis
| Autor: | David A. Sinclair, Haim Y. Cohen, Roy A. Frye, Benedikt M. Kessler, Brian G Hekking, Siva Lavu, Thomas A Imahiyerobo, Kevin J. Bitterman, Christine M. Miller, Hidde L. Ploegh |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Molecular Sequence Data Apoptosis Biology Mitochondrion Mice Bcl-2-associated X protein In vivo Acetyltransferases Cricetinae Proto-Oncogene Proteins Animals Humans Amino Acid Sequence CREB-binding protein Enzyme Inhibitors Molecular Biology Ku Autoantigen Histone Acetyltransferases bcl-2-Associated X Protein Ku70 Binding Sites Sequence Homology Amino Acid Lysine Tumor Suppressor Proteins DNA Helicases Nuclear Proteins Acetylation Antigens Nuclear Cell Biology Molecular biology CREB-Binding Protein Protein Structure Tertiary DNA-Binding Proteins PCAF Proto-Oncogene Proteins c-bcl-2 biology.protein Trans-Activators HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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