期刊
NATURE CELL BIOLOGY
卷 11, 期 5, 页码 580-U122出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1864
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资金
- Chinese National Basic Research Programs [2007CB914601, 2006CB910802]
- Chinese National Natural Science Foundation [30621063, 30600310, 30871373]
- Beijing Science and Technology NOVA Program [2007A063]
Only a few p53 regulators have been shown to participate in the selective control of p53-mediated cell cycle arrest or apoptosis. How p53-mediated apoptosis is negatively regulated remains largely unclear. Here we report that Apak (ATM and p53-associated KZNF protein), a Kruppel-associated box (KRAB)-type zinc-finger protein, binds directly to p53 in unstressed cells, specifically downregulates pro-apoptotic genes, and suppresses p53-mediated apoptosis by recruiting KRAB-box-associated protein (KAP)-1 and histone deacetylase 1 (HDAC1) to attenuate the acetylation of p53. Apak inhibits p53 activity by interacting with ATM, a previously identified p53 activator. In response to stress, Apak is phosphorylated by ATM and dissociates from p53, resulting in activation of p53 and induction of apoptosis. These findings revealed Apak to be a negative regulator of p53-mediated apoptosis and showed the dual role of ATM in p53 regulation.
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