当BH3配体与多个Bcl-2同源物而非Bax或Bak结合时，细胞凋亡启动。
Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak.
作者信息
Willis Simon N, Fletcher Jamie I, Kaufmann Thomas, van Delft Mark F, Chen Lin, Czabotar Peter E, Ierino Helen, Lee Erinna F, Fairlie W Douglas, Bouillet Philippe, Strasser Andreas, Kluck Ruth M, Adams Jerry M, Huang David C S
机构信息
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
出版信息
Science. 2007 Feb 9;315(5813):856-9. doi: 10.1126/science.1133289.
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.
Bcl-2家族对细胞凋亡的调控中的一个核心问题是，其仅含BH3结构域的成员是通过直接结合关键的细胞死亡介质Bax和Bak来启动细胞凋亡，还是通过与它们的促生存Bcl-2样相关蛋白相互作用来间接发挥作用。与直接激活模型相反，我们发现，即使在没有Bim或Bid且Puma减少的细胞中，Bax和Bak也能介导细胞凋亡，而与假定的仅含BH3结构域的激活因子（Bim、Bid和Puma）没有明显关联。我们的结果表明，仅含BH3结构域的蛋白至少主要是通过与守护Bax和Bak的多种促生存相关蛋白相互作用来诱导细胞凋亡。
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