Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE

Cell. 1998 Feb 20;92(4):501-9. doi: 10.1016/s0092-8674(00)80943-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspase 1
  • Caspases*
  • Caspases, Initiator
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / enzymology
  • Embryonic and Fetal Development
  • Endopeptidases / genetics*
  • Endopeptidases / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutagenesis
  • Shock, Septic / metabolism

Substances

  • Endopeptidases
  • Casp4 protein, mouse
  • Caspases
  • Caspases, Initiator
  • Cysteine Endopeptidases
  • Caspase 1