Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
摘要：
Activation of procaspase-9 by Apaf-1 in the cytochrome c/dATP-dependent pathway requires proteolytic cleavage to generate the mature caspase molecule. To elucidate the mechanism of activation of procaspase-9 by Apaf-1, we designed an in vitro Apaf-1-procaspase-9 activation system using recombinant components. Here, we show that deletion of the Apaf-1 WD-40 repeats makes Apaf-1 constitutively active and capable of processing procaspase-9 independent of cytochrome c an dATP. Apaf-1-mediated processing of procaspase-9 occurs at Asp-315 by an intrinsic autocatalytic activity of procaspase-9 itself. We provide evidence that Apaf-1 can form oligomers and may facilitate procaspase-9 autoactivation by oligomerizing its precursor molecules. Once activated, caspase-9 can initiate a caspase cascade involving the downstream executioners caspase-3, -6, and -7.
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关键词：
Humans Tumor Cells, Cultured Biopolymers Cytochrome c Group Enzyme Precursors Cysteine Endopeptidases Caspases Adenosine Triphosphate Proteins Recombinant Proteins
DOI：
10.1016/S1097-2765(00)80095-7
被引量：
年份：
1998
Elsevier
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