Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage
Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage
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DOI：
10.1016/j.bbrc.2005.05.126
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发表时间：
2005-07-29
影响因子：
3.1
通讯作者：
Motoyama, N
中科院分区：
文献类型：
--
作者：
Chen, C;Shimizu, S;Motoyama, N
肿瘤抑制蛋白 p53 在响应基因毒性应激而诱导细胞凋亡中发挥着核心作用。蛋白激酶 Chk2 是暴露于电离辐射 (IR) 的哺乳动物细胞中 p53 功能的重要调节因子。来自 Chk2 缺陷小鼠的细胞对 IR 诱导的细胞凋亡具有抵抗力，这种抵抗力被认为是 p53 靶基因转录激活缺陷的结果。然而，最近的研究表明，p53 本身和组蛋白 H1.2 易位至线粒体，从而响应 IR 以转录独立的方式诱导细胞凋亡。我们现在检查了 Chk2 是否也调节 p53 和历史 H1.2 的转录非依赖性细胞凋亡诱导。在 Chk2 缺陷的胸腺细胞中，IR 诱导 p53 稳定的能力降低与 p53 的显着损伤和历史上 HI 易位至线粒体有关。这些结果表明 Chk2 通过诱导 p53 响应 IR 的稳定性来调节 p53 介导的细胞凋亡的转录独立机制。 (c) 2005 Elsevier Inc. 保留所有权利。
The tumor suppressor protein p53 plays a central role in the induction of apoptosis in response to genotoxic stress. The protein kinase Chk2 is an important regulator of p53 function in mammalian cells exposed to ionizing radiation (IR). Cells derived from Chk2-deficient mice are resistant to the induction of apoptosis by IR, and this resistance has been thought to be a result of the defective transcriptional activation of p53 target genes. It was recently shown, however, that p53 itself and histone H1.2 translocate to mitochondria and thereby induces apoptosis in a transcription-independent manner in response to IR. We have now examined whether Chk2 also regulates the transcription-independent induction of apoptosis by p53 and historic H1.2. The reduced ability of IR to induce p53 stabilization in Chk2-deficient thymocytes was associated with a marked impairment of p53 and historic HI translocation to mitochondria. These results suggest that Chk2 regulates the transcription-independent mechanism of p53-mediated apoptosis by inducing stabilization of p53 in response to IR. (c) 2005 Elsevier Inc. All rights reserved.