Nature 385, 653 - 656 (13 February 1997); doi:10.1038/385653a0

Interaction between the C. elegans cell-death regulators CED-9 and CED-4

Mona S. Spector^*, Serge Desnoyers^*, Daniel J. Hoeppner^*† & Michael O. Hengartner^*

^* Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
^† Graduate Program in Genetics, Department of Molecular Microbiology, SUNY at Stony Brook, Stony Brook, New York 11794, USA

Programmed cell death (apoptosis) is an evolutionarily conserved process used by multicellular organisms to eliminate cells that are not needed or are potentially detrimental to the organism^1,2. Members of the Bcl-2 family of mammalian proteins are intimately involved in the regulation of apoptosis, but, their precise mechanism of action remains unresolved^3–5. In Caenorhabditis elegans, the Bcl-2 homologue CED-9 prevents cell death by antagonizing the death-promoting activities of CED-3, a member of the Caspase family of death proteases, and of CED-4, a protein with no known mammalian homologue^6–9. Here we show that CED-9 interacts physically with CED-4. Mutations that reduce or eliminate CED-9 activity also disrupt its ability to bind CED-4, suggesting that this interaction is important for CED-9 function. Thus, CED-9 might control C. elegans cell death by binding to and regulating CED-4 activity. We propose that mammalian Bcl-2 family members might control apoptosis in a similar way through interaction and regulation of CED-4 homologues or analogues.

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