KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis
KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis
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DOI：
10.1038/ncb1864
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发表时间：
2009-05-01
影响因子：
21.3
通讯作者：
He, Fuchu
中科院分区：
文献类型：
--
作者：
Tian, Chunyan;Xing, Guichun;He, Fuchu
只有少数的P53调节因子参与选择性地控制P53介导的细胞周期停滞或凋亡。P53介导的细胞凋亡是如何被负调控的，目前仍不清楚。Apak(ATM和P53相关的KZNF蛋白)是一种Kruppel相关盒(KRAb)类型的锌指蛋白，在非应激细胞中直接与P53结合，特异性地下调促凋亡基因，并通过招募KRAb-box相关蛋白(KAP)-1和组蛋白去乙酰化酶1(HDAC1)来抑制P53的乙酰化，从而抑制P53介导的凋亡。APAK通过与ATM相互作用来抑制P53的活性，ATM是一种先前发现的P53激活剂。在应激反应中，APAK被ATM磷酸化，并与P53解离，导致P53激活并诱导细胞凋亡。这些发现揭示了APAK是P53介导的细胞凋亡的负调控因子，并显示了ATM在P53调节中的双重作用。
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.