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. 1998 Jun;1(7):949-57.
doi: 10.1016/s1097-2765(00)80095-7.

Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization

S M Srinivasula  1 , M Ahmad, T Fernandes-Alnemri, E S Alnemri
Affiliations
Free article

Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization

S M Srinivasula et al. Mol Cell. 1998 Jun.
Free article

Abstract

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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