THE C-ELEGANS PROTEIN EGL-1 IS REQUIRED FOR PROGRAMMED CELL-DEATH ANDINTERACTS WITH THE BCL-2-LIKE PROTEIN CED-9

Gain-of-function mutations in the Caenorhabditis elegans gene egl-1 ca use the HSN neurons to undergo programmed cell death. By contrast, a l oss-of-function egl-1 mutation prevents most if not all somatic progra mmed cell deaths. The egl-1 gene negatively regulates the ced-9 gene, which protects against cell death and is a member of the bcl-2 family. The EGL-1 protein contains a nine amino acid region similar to the Bc l-2 homology region 3 (BH3) domain but does not contain a BH1, BH2, or BH4 domain, suggesting that EGL-1 may be a member of a family of cell death activators that includes the mammalian proteins Bik, Bid, Harak iri, and Bad. The EGL-1 and CED-9 proteins interact physically. We pro pose that EGL-1 activates programmed cell death by binding to and dire ctly inhibiting the activity of CED-9, perhaps by releasing the cell d eath activator CED-4 from a CED-9/CED-4-containing protein complex.