Oligomerization and activation of caspase-9, induced by Apaf-1 CARD.
نویسندگان
چکیده
Apaf-1 facilitates the proteolytic activation of procaspase-9 and maintains the hyperactive state of the processed caspase-9. The underlying molecular mechanisms for these activities remain poorly characterized. Here we report that the isolated Apaf-1 caspase recruitment domain (CARD) forms a large hetero-oligomer with the active caspase-9. The catalytic activity of caspase-9 is significantly enhanced in this complex, demonstrating that Apaf-1 CARD allosterically up-regulates caspase-9 activity. Point mutations that inactivate the interactions between Apaf-1 CARD and the prodomain of caspase-9 also abolished the formation of this complex. Based on these observations, we discuss the implications of this complex on the observed Apaf-1 function.
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 99 7 شماره
صفحات -
تاریخ انتشار 2002