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
Allosteric regulationBiologyCaspaseCell biologyProtein subunitRegulatorCaspase-9Enzyme activatorApoptosisCaspase 7Caspase 2BiochemistryEnzymeSignal transductionProgrammed cell deathGene
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Publication Info
- Year
- 1999
- Type
- article
- Volume
- 13
- Issue
- 24
- Pages
- 3179-3184
- Citations
- 562
- Access
- Closed
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Cite This
Joe Rodriguez,
Yuri Lazebnik
(1999).
Caspase-9 and APAF-1 form an active holoenzyme.
Genes & Development
, 13
(24)
, 3179-3184.
https://doi.org/10.1101/gad.13.24.3179
Identifiers
- DOI
- 10.1101/gad.13.24.3179