Oncogene-dependent apoptosis is mediated by caspase-9
Oncogene-dependent apoptosis is mediated by caspase-9
复制标题
DOI：
10.1073/pnas.95.23.13664
复制
发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Lazebnik, YA
中科院分区：
文献类型：
--
作者：
Fearnhead, HO;Rodriguez, J;Lazebnik, YA
了解致癌转化如何使细胞对凋亡敏感，可能为选择性杀伤肿瘤细胞提供一种策略。我们以前开发了一个无细胞系统，它概括了癌基因依赖性的凋亡，这反映在caspase的激活上，caspase是凋亡机制的核心。在这里，我们表明，这种激活需要一个先前发现的由caspase-9，apaf-1和细胞色素c组成的促凋亡复合体。正如体外系统预测的那样，阻止caspase-9的激活可以阻断药物诱导的BG E1A(腺病毒癌基因)致敏的细胞的凋亡。癌基因，如E1a，似乎通过几种机制促进caspase-9的激活，包括控制细胞色素c从线粒体释放。
Understanding how oncogenic transformation sensitizes cells to apoptosis may provide a strategy to kill tumor cells selectively. We previously developed a cell-free system that recapitulates oncogene dependent apoptosis as reflected by activation of caspases, the core of the apoptotic machinery. Here, we show that this activation requires a previously identified apoptosis-promoting complex consisting of caspase-9, APAF-1, and cytochrome c. As predicted by the in vitro system, preventing caspase-9 activation blocked drug-induced apoptosis in cells sensitized bg E1A, an adenoviral oncogene. Oncogenes, such as E1A, appear to facilitate caspase-9 activation by several mechanisms, including the control of cytochrome c release from the mitochondria.