Bak but not Bax is essential for Bcl-xs-induced apoptosis
Bak but not Bax is essential for Bcl-xs-induced apoptosis
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DOI：
10.1038/sj.cdd.4401638
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发表时间：
2005-07-01
影响因子：
12.4
通讯作者：
Stein, R
中科院分区：
文献类型：
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作者：
Lindenboim, L;Kringel, S;Stein, R
Bcl-2蛋白家族的促凋亡成员Bcl-x（S）定位于线粒体中，并通过涉及细胞色素c释放的机制以半胱天冬酶和BH 3依赖性方式诱导细胞凋亡。Bcl-x（S）诱导半胱天冬酶活化和细胞色素c释放的方式，以及Bcl-x（S）与Bcl-2家族的其他促凋亡成员之间的关系尚不清楚。在此，我们使用了来自缺乏Bcl-2家族多结构域促凋亡成员（Bax和巴克）和凋亡小体的凋亡组分（Apaf-1和caspase-9）的小鼠的胚胎成纤维细胞，以阐明Bcl-x（S）促进凋亡的级联反应。我们的结果表明，巴克，而不是Bax是必不可少的Bcl-x（S）诱导的细胞凋亡。Bcl-x（S）可诱导巴克活化，而巴克活化又可通过线粒体依赖性和非依赖性途径促进细胞凋亡。这些发现提供了第一个证据，证明促细胞凋亡Bcl-2家族蛋白仅通过巴克诱导细胞凋亡。
Bcl-x(S), a proapoptotic member of the Bcl-2 protein family, is localized in the mitochondria and induces apoptosis in a caspase-and BH3-dependent manner by a mechanism involving cytochrome c release. The way in which Bcl-x(S) induces caspase activation and cytochrome c release, as well as the relationship between Bcl-x(S) and other proapoptotic members of the Bcl-2 family, is not known. Here we used embryonic fibroblasts derived from mice deficient in the multidomain proapoptotic members of the Bcl-2 family (Bax and Bak) and the apoptotic components of the apoptosome (Apaf-1 and caspase-9) to unravel the cascade of events by which Bcl-x(S) promotes apoptosis. Our results show that Bak but not Bax is essential for Bcl-x(S)-induced apoptosis. Bcl-x(S) induced activation of Bak, which in turn promoted apoptosis by apoptosome-dependent and -independent pathways. These findings provide the first evidence that a proapoptotic Bcl-2 family protein induces apoptosis exclusively via Bak.