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Science 28 August 1998:
Vol. 281. no. 5381, pp. 1355 - 1357
DOI: 10.1126/science.281.5381.1355
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Reports

Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis

Xiaolu Yang, * Howard Y. Chang, David Baltimore dagger

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.

X. Yang and H. Y. Chang, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. D. Baltimore, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, and California Institute of Technology, Pasadena, CA 91125, USA.
*   Present address: Department of Molecular and Cellular Engineering and Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

dagger    To whom correspondence should be addressed.

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