Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
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DOI：
10.1016/j.ccr.2006.03.027
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发表时间：
2006-05-01
期刊：
影响因子：
50.3
通讯作者：
Letai, Anthony
中科院分区：
文献类型：
--
作者：
Certo, Michael;Moore, Victoria Del Gaizo;Letai, Anthony
我们表明，抗凋亡蛋白BCL - 2、BCL - XL、MCL - 1、BFL - 1和BCL - w各自与一组源自仅含BH3结构域蛋白的BH3结构域的肽段具有独特的相互作用模式。细胞对某一抗凋亡蛋白的生存依赖性可根据线粒体对这组肽段的敏感性模式来解读，我们将这种策略称为BH3谱分析。对抗凋亡蛋白的依赖性与抗凋亡蛋白对激活型仅含BH3结构域蛋白（如BID或BIM）的隔离相关。对细胞可渗透的BCL - 2拮抗剂ABT - 737的敏感性也与激活型仅含BH3结构域分子对BCL - 2的激活相关。我们的数据使我们能够区分一种我们称为“死亡致敏”的细胞状态，这种状态可通过BH3谱分析确定，并且与细胞生存对抗凋亡家族成员的依赖性相关。
We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by 131143 profiling and which correlates with dependence on antiapoptotic family members for survival.