THE CAENORHABDITIS-ELEGANS DEATH PROTEIN CED-4 CONTAINS A MOTIF WITH SIMILARITY TO THE MAMMALIAN DEATH EFFECTOR DOMAIN

In the nematode Caenorhabditis elegans apoptosis is tightly regulated by a hierarchical set of genes. Two of these, ced-3 and ced-9, possess mammalian homologues encoding executional ICE proteases and inhibitor y Bcl-2-related proteins, respectively. The function of a third key pl ayer, ced-4, is however completely unknown and no mammalian counterpar ts have been identified. Here me report that Ced-4 protein contains a structural region with similarity to the mammalian death effector doma in which has previously been demonstrated to act as an important prote in interaction motif in the signaling pathway of the mammalian surface receptor Fas (APO-1, CD95). Based on this finding and previously desc ribed genetic experiments, we propose that Ced-4, similar to the mamma lian proteins FADD and FLICE, may possess a function as an adaptor pro tein in invertebrate apoptotic pathways.