Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
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DOI：
10.1016/s0092-8674(00)80434-1
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发表时间：
1997-11-14
期刊：
影响因子：
64.5
通讯作者：
Wang, XD
中科院分区：
文献类型：
--
作者：
Li, P;Nijhawan, D;Wang, XD
我们在这里报告的第三个蛋白质因子，Apaf-3，在体外参与半胱天冬酶-3激活的纯化。Apaf-3被鉴定为caspase-9家族的成员。在细胞色素c和dATP存在下，胱天蛋白酶-9和Apaf-1通过其各自的NH 2-末端CED-3同源结构域彼此结合，这是导致胱天蛋白酶-9活化的事件。活化的半胱天冬酶-9继而切割并活化半胱天冬酶-3。S-100提取物中caspase-9的耗尽减少了caspase-3的活化。caspase-9活性位点的突变减弱了caspase-3的激活和体内细胞凋亡反应，表明caspase-9是细胞色素c和dATP触发的凋亡蛋白酶级联反应的最上游成员。
We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.