Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE.
We report here the inactivation of a member of the Ice/Ced-3 (caspase) family of cell death genes, casp-11, by gene targeting. Like Ice-deficient mice, casp-11 mutant mice are resistant to endotoxic shock induced by lipopolysaccharide. Production of both IL-1alpha and IL-1beta after lipopolysaccharide stimulation, a crucial event during septic shock and an indication of ICE activation, is blocked in casp-11 mutant mice. casp-11 mutant embryonic fibroblast cells are resistant to apoptosis induced by overexpression of ICE. Furthermore, we found that pro-caspase-11 physically interacts with pro-ICE in cells, and the expression of casp-11 is essential for activation of ICE. Our data suggest that caspase-11 is a component of ICE complex and is required for the activation of ICE.
Pubmed ID: 9491891 RIS Download
Animals | Apoptosis | Caspase 1 | Caspases | Cells, Cultured | Cysteine Endopeptidases | Embryo, Mammalian | Embryonic and Fetal Development | Endopeptidases | Enzyme Activation | Gene Expression Regulation, Developmental | Gene Expression Regulation, Enzymologic | Mice | Mice, Inbred C57BL | Mice, Mutant Strains | Mutagenesis | Shock, Septic