Caspase-9 and APAF-1 form an active holoenzyme

  1. Joe Rodriguez and
  2. Yuri Lazebnik
  1. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA; Molecular and Cell Biology Graduate Program, State University of New York at Stony Brook, Stony Brook, New York 11733 USA

Abstract

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.

Keywords

Footnotes

  • Corresponding author.

  • E-MAIL lazebnik{at}cshl.org; FAX (516) 367-8461.

    • Received July 12, 1999.
    • Accepted November 1, 1999.
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