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 inhibitory Bcl-2-related proteins, respectively. The function of a third key player, ced-4, is however completely unknown and no mammalian counterparts have been identified. Here we report that Ced-4 protein contains a structural region with similarity to the mammalian death effector domain which has previously been demonstrated to act as an important protein interaction motif in the signaling pathway of the mammalian surface receptor Fas (APO-1, CD95). Based on this finding and previously described genetic experiments, we propose that Ced-4, similar to the mammalian proteins FADD and FLICE, may possess a function as an adaptor protein in invertebrate apoptotic pathways.