CELL-DEATH IN C-ELEGANS - MOLECULAR INSIGHTS INTO MECHANISMS CONSERVED BETWEEN NEMATODES AND MAMMALS

As is the case for most metazoans, C. elegans cells have the potential to undergo developmental cell death (programmed cell death) or a necr otic-like death in response to cell injury. Analysis of mutations that disrupt the reproducible pattern of cell death that occurs during C. elegans development has defined a genetic pathway for programmed cell death. This program involves the activities of certain genes, such as ces-1 and the ces-2 bZIP transcription faster, which regulate the life /death decision in specific subsets of cells, ced-9, a Bcl-2 family me mber, acts globally to negatively regulate the activities of ced-4S (w hich promotes cell death) and ced-4L, which promotes cell life. ced-3 encodes a member of the ICE cysteine protease family that is essential for execution of all programmed cell deaths. Once cells die, corpses are phagocytized and consumed in what appear to be at least two parall el pathways that require the activities of ced-1, ced-6, ced-7 and ced -2, ced-5, ced-10. Degradation of corpse DNA requires the product of t he nuc-1 gene. Degenerative cell death, characterized by cell swelling , can be induced by different cell injuries including that conferred b y mutant degenerin ion channels (encoded by deg-1, mec-4, mec-10 and u nc-8) and by expression of human beta-amyloid peptide. Remarkable para llels between nematode and mammalian death programs have advanced unde rstanding of human cell death mechanisms.