Abstract
Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans , the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2–like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.
Keywords
Caenorhabditis elegansCell biologyApoptosisChemistryIn vitroZymogenCaspaseProgrammed cell deathBiologyBiochemistryEnzymeGene
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Publication Info
- Year
- 1998
- Type
- article
- Volume
- 281
- Issue
- 5381
- Pages
- 1355-1357
- Citations
- 267
- Access
- Closed
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Cite This
Xiaolu Yang,
Howard Y. Chang,
David Baltimore
(1998).
Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis.
Science
, 281
(5381)
, 1355-1357.
https://doi.org/10.1126/science.281.5381.1355
Identifiers
- DOI
- 10.1126/science.281.5381.1355