ERICE, a Novel FLICE-activatable Caspase

We report here the cloning and characterization of a novel member of the ICE subfamily termed ERICE for Evolutionarily Related ICE

Eric W. Humke; Jian Ni; Vishva M. Dixit

2002

Scholarcy highlights

  • Apoptosis, or programmed cell death, is an evolutionarily conserved process central to the normal development and homeostasis of multicellular organisms
  • Genetic analysis of the nematode Caenorhabditis elegans has revealed three core components of the death pathway, ced-3, ced-4, and ced-9 . ced-3 and ced-4 are death genes, and mutations in either attenuate the elimination of cells that normally die during worm development
  • These central players of cell death in the nematode are conserved in vertebrates
  • Hydrophobic amino acids are not found in the P4 position of substrates known to be cleaved during cell death
  • ERICE Is a Novel Member of the Caspase Gene Family—The full-length 2.2-kilobase ERICE cDNA contained an open reading frame of 377 amino acids encoding a protein of predicted molecular mass 43.0 kDa
  • The sequence homology is very high between ERICE and caspases-4 and -5, residues that make up the P2–P4 binding pocket are not conserved, suggesting a different substrate specificity
  • This is the first example of an ICE subfamily member that is activated by caspase-8 and suggests a potential downstream role for active ERICE in caspase-8-mediated cell death

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