A phylogenetic and functional overview of inflammatory caspases and caspase-1-related CARD-only proteins.
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.
Kersse
K
K
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Vanden Berghe
T
T
Lamkanfi
M
M
Vandenabeele
P
P
D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000276:immunology*; D020169:Caspases / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D010802:Phylogeny
D053468:CARD Signaling Adaptor Proteins; D016328:NF-kappa B; D020169:Caspases