Apak 与 p53 竞争直接结合到 p53AIP1 的内含子 1 上以调节细胞凋亡。
Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis.
机构信息
Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui Province 230032, China.
出版信息
EMBO Rep. 2012 Apr;13(4):363-70. doi: 10.1038/embor.2012.10.
Abstract
The KRAB-type zinc-finger protein Apak was recently identified as a negative regulator of p53-mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN2−30TTGT consensus sequence through its zinc-fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53-binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53-mediated apoptosis.
摘要
KRAB 型锌指蛋白 Apak 最近被鉴定为 p53 介导的细胞凋亡的负调控因子。然而，这种选择性调节的机制尚不完全清楚。在这里，我们表明 Apak 通过其锌指识别 TCTTN2−30TTGT 共识序列。该序列专门存在于促凋亡 p53 靶基因 p53AIP1 的内含子 1 中，并且与 p53 结合序列大部分重叠。Apak 与 p53 竞争结合该位点以抑制 p53AIP1 的表达。在 DNA 损伤时，Apak 从 DNA 上解离，从而消除其对 p53 介导的细胞凋亡的抑制作用。
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