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.
Wang
S
S
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Miura
M
M
Jung
Y K
YK
Zhu
H
H
Li
E
E
Yuan
J
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020170:Caspase 1; D020169:Caspases; D053471:Caspases, Initiator; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology; D005314:Embryonic and Fetal Development; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D012772:Shock, Septic / Q000378:metabolism
D010450:Endopeptidases; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases; D020170:Caspase 1