Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak
Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak
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DOI：
10.1126/science.1133289
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发表时间：
2007-02-09
期刊：
影响因子：
56.9
通讯作者：
Huang, David C. S.
中科院分区：
文献类型：
--
作者：
Willis, Simon N.;Fletcher, Jamie I.;Huang, David C. S.
Bcl-2家族调控细胞凋亡的一个核心问题是，其仅bh3成员是通过直接结合必需的细胞死亡介质Bax和Bak启动细胞凋亡，还是通过参与其促存活的Bcl-2样亲属间接起作用。与直接激活模型相反，我们发现Bax和Bak可以介导细胞凋亡，而与假定的仅bh3激活因子（Bim、Bid和Puma）没有明显的关联，即使在没有Bim或Bid和Puma减少的细胞中也是如此。我们的研究结果表明，BH3-only蛋白诱导细胞凋亡至少主要是通过参与保护Bax和Bak的多个促存活亲缘蛋白。
A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.