Article abstract
Nature Cell Biology 11, 580 - 591 (2009)
Published online: 19 April 2009 | doi:10.1038/ncb1864
KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis
Chunyan Tian1, Guichun Xing1, Ping Xie1,2, Kefeng Lu1, Jing Nie1,2, Jian Wang1, Li Li1, Mei Gao1, Lingqiang Zhang1 & Fuchu He1,2,3
Abstract
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 Krüppel-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.
- State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
- Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
- Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Correspondence to: Lingqiang Zhang1Fuchu He1,2,3 e-mail: zhanglq@nic.bmi.ac.cn
Correspondence to: e-mail: hefc@nic.bmi.ac.cn
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