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Vol. 13, No. 24, pp. 3179-3184, December 15, 1999
1 Cold Spring Harbor Laboratory, Cold Spring Harbor, New
York 11724 USA; 2 Molecular and Cell Biology Graduate Program,
State University of New York at Stony Brook,
Stony Brook, New York 11733 USA
Autocatalytic activation of initiator caspases is the link between
pro-apoptotic signals and the destruction machinery of apoptosis.
Activation of caspase-9, which mediates oncogene and drug-induced
apoptosis, requires binding to the protein APAF-1. We found that the
proteolytic activity of caspase-9 in a complex with APAF-1 is several
orders of magnitude higher than that of the free enzyme. Thus, this
complex functions as a holoenzyme in which caspase-9 is the catalytic
subunit and APAF-1 its allosteric regulator. We argue that caspase-9 is
activated by allosteric regulation and suggest that this mechanism is
common for other initiator caspases.
[Key Words: Apoptosis; cancer; caspases; capase-9; APAF-1]
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