INDUCTION OF APOPTOSIS IN FIBROBLASTS BY IL-1-BETA-CONVERTING ENZYME, A MAMMALIAN HOMOLOG OF THE C-ELEGANS CELL-DEATH GENE CED-3

The mammalian interleukin-1beta-converting enzyme (ICE) has sequence similarity to the C. elegans cell death gene ced-3. We show here that overexpression of the murine ICE (mICE) gene or of the C. elegans ced-3 gene causes Rat-1 cells to undergo programmed cell death. Point mutations in a region homologous between mICE and CED-3 eliminate the ability of mICE and ced-3 to cause cell death. The cell death caused by mICE can be suppressed by overexpression of the crmA gene, a specific inhibitor of ICE, as well as by bcl-2, a mammalian oncogene that can act to prevent programmed cell death. Our results suggest that ICE may function during mammalian development to cause programmed cell death.