Essential role for caspase-8 in transcription-independent apoptosis triggered by p53
Essential role for caspase-8 in transcription-independent apoptosis triggered by p53
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DOI：
10.1074/jbc.m004714200
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发表时间：
2000-12-08
影响因子：
4.8
通讯作者：
Fisher, DE
中科院分区：
文献类型：
--
作者：
Ding, HF;Lin, YL;Fisher, DE
p53 对细胞凋亡的双重调节可能是抗癌治疗的肿瘤选择性作用的基础。 p53 的细胞凋亡效应被认为涉及转录依赖性和非转录依赖性机制。这里显示，caspase-8 在经历 p53 介导的细胞凋亡的细胞和概括转录无关细胞凋亡的 S100 无细胞提取物中早期被激活，细胞或无细胞提取物中 caspase-8 的耗尽或失活完全阻止了这种转录无关细胞凋亡，并显着减弱野生型 p53 诱导的总体死亡。重要的是，caspase-8 的激活似乎与 FADD 无关，并且在 p53 激活后，在一种新型 600 kDa 复合物中发现了 caspase-8。这些发现强调了 p53 对转录依赖性和非依赖性细胞凋亡的作用，并确定了 caspase-8 在转录非依赖性途径中的重要作用。
p53's dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and -independent mechanisms. It is shown here that caspase-8 is activated early in cells undergoing p53-mediated apoptosis and in S100 cell-free extracts that recapitulate transcription-independent apoptosis, Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wildtype p53. Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway.