Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1
Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1
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DOI：
10.1016/s1097-2765(00)00005-8
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发表时间：
2000-07-01
期刊：
影响因子：
16
通讯作者：
Hardwick, JM
中科院分区：
文献类型：
--
作者：
Chau, BN;Cheng, EHY;Hardwick, JM
Bcl-x（L）是一种抗凋亡Bcl-2家族成员，被认为在细胞死亡途径的多个阶段发挥作用。Bcl-x（L）在死亡途径的晚期（线粒体后）步骤抑制细胞死亡的可能性得到了一种新型凋亡抑制剂Aven的报告的支持，Aven与Bcl-x（L）和半胱天冬酶调节剂Apaf-1结合。在酵母双杂交筛选中鉴定，Aven在其他哺乳动物物种中广泛表达并保守。只有那些保留其抗凋亡活性的Bcl-x（L）突变体才能结合Aven。Aven干扰Apaf-1自我缔合的能力，表明Aven损害Apaf-1介导的半胱天冬酶激活。与这一想法一致，Aven抑制了无细胞提取物中caspase的蛋白水解活化，并抑制了Apaf-1加caspase-9诱导的细胞凋亡。因此，Aven代表了一类新的细胞死亡调节剂。
Bcl-x(L), an antiapoptotic Bcl-2 family member, is postulated to function at multiple stages in the cell death pathway. The possibility that Bcl-x(L) inhibits cell death at a late (postmitochondrial) step in the death pathway is supported by this report of a novel apoptosis inhibitor, Aven, which binds to both Bcl-x(L) and the caspase regulator, Apaf-1. Identified in a yeast two-hybrid screen, Aven is broadly expressed and is conserved in other mammalian species. Only those mutants of Bcl-x(L) that retain their antiapoptotic activity are capable of binding Aven. Aven interferes with the ability of Apaf-1 to self-associate, suggesting that Aven impairs Apaf-1-mediated activation of caspases. Consistent with this idea, Aven inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by Apaf-1 plus caspase-9. Thus, Aven represents a new class of cell death regulator.