Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis
SciencePublished 28 August 1998
Xiaolu Yang, Howard Y. Chang, David Baltimore
Citations267
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
Control of the activation of apoptosis is important both in development and in protection against cancer and Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death.
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
Biochemistry, Genetics and Molecular Biology
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