A phylogenetic and functional overview of inflammatory caspases and caspase-1-related CARD-only proteins

Biochem Soc Trans. 2007 Dec;35(Pt 6):1508-11. doi: 10.1042/BST0351508.

Abstract

Caspase 1 is a cysteinyl aspartate-specific proteinase involved in the maturation of inflammatory cytokines such as pro-IL-1beta (interleukin-1beta) and pro-IL-18. Caspase 1 clusters phylogenetically together with human caspases 4, 5 and 12 and murine caspases 11 and 12, and forms the group of the so-called inflammatory caspases. Caspase 1 consists of an N-terminal CARD (caspase recruitment domain) and a proteolytic domain containing the catalytic residues. The CARD-containing prodomain is involved in the formation of the protease-activating inflammasome complex. We have also found that the prodomain is necessary and sufficient for the activation of NF-kappaB (nuclear factor kappaB). The human genome also contains three caspase-1-related CARD-only decoy proteins [COP (CARD-only protein), INCA (inhibitory CARD) and ICEBERG], which are located near the caspase 1 locus. In this mini-review, we focus on the evolutionary aspects of the inflammatory caspase locus in the human, chimpanzee, Rhesus monkey, mouse and rat. Furthermore, we discuss the functional characteristics of the caspase-1-related CARD-only proteins in relation to caspase-1-mediated IL-1beta maturation and NF-kappaB activation.

Publication types

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

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / genetics*
  • CARD Signaling Adaptor Proteins / immunology*
  • Caspases / genetics*
  • Caspases / immunology*
  • Humans
  • Inflammation / enzymology
  • Inflammation / immunology
  • NF-kappa B / immunology
  • Phylogeny

Substances

  • CARD Signaling Adaptor Proteins
  • NF-kappa B
  • Caspases