c-jun downregulation by HDAC3-dependent transcriptional repression promotes osmotic stress-induced cell apoptosis
c-jun downregulation by HDAC3-dependent transcriptional repression promotes osmotic stress-induced cell apoptosis
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DOI：
10.1016/j.molcel.2007.01.005
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发表时间：
2007-01-26
期刊：
影响因子：
16
通讯作者：
Lu, Zhimin
中科院分区：
文献类型：
--
作者：
Xia, Yan;Wang, Ji;Lu, Zhimin
c-Jun 是调节蛋白激活蛋白 1 (AP-1) 家族中的主要转录因子，可被许多生理和病理刺激激活。然而，c-jun是否受到染色质结构表观遗传修饰的调节尚不清楚。我们在此表明，c-jun 通过天冬氨酸 391 处 caspase-7 依赖性裂解产生的截短 HDAC3 响应渗透应激而受到转录抑制。 caspase-7 的激活独立于细胞色素 c 的释放以及 caspase-9 和 caspase-12 的激活，依赖于 caspase-8 的激活，而 caspase-8 反过来需要 MEK2 活性和 FAS 配体的分泌。渗透胁迫期间由截短的 HDAC3 诱导的或由 c-Jun 缺乏增强的细胞凋亡被 c-Jun 的外源表达抑制，表明 HDAC3 依赖性转录抑制对 c-Jun 的下调在调节细胞存活和凋亡中发挥作用。
c-Jun, a major transcription factor in the activating protein 1 (AP-1) family of regulatory proteins, is activated by many physiologic and pathologic stimuli. However, whether c-jun is regulated by epigenetic modification of chromatin structure is not clear. We showed here that c-jun was transcriptionally repressed in response to osmotic stress via a truncated HDAC3 generated by caspase-7-dependent cleavage at aspartic acid 391. The activation of caspase-7, which is independent of cytochrome c release and activation of caspase-9 and caspase-12, depends on activation of caspase-8, which in turn requires MEK2 activity and secretion of FAS ligand. The cell apoptosis induced by the truncated HDAC3 or enhanced by c-Jun deficiency during osmotic stress was suppressed by exogenous expression of c-Jun, indicating that the down-regulation of c-Jun by HDAC3-dependent transcriptional repression plays a role in regulating cell survival and apoptosis.