title: Caspase-containing complexes in the regulation of cell death and inflammation.
abstract: Caspases are a family of cysteine proteases that are essential in the initiation and execution of apoptosis and the proteolytic maturation of inflammatory cytokines such as IL-1beta and IL-18. Caspases can be subdivided into those that have a large prodomain and those that have not. In general, apoptotic and inflammatory signalling pathways are initiated when large-prodomain caspases are recruited to large protein complexes via homotypic interactions involving death domain folds. The formation of these specialised multimeric platforms involves three major functions: (1) the sensing of cellular stress, damage, infection or inflammation; (2) multimerisation of the platform; and (3) recruitment and conformational activation of caspases. In this overview we discuss the complexes implicated in the regulation of cell death and inflammatory processes such as the death-inducing signalling complex (DISC), the apoptosome, the inflammasomes and the PIDDosome. We describe their sensing functions, compositions and functional outcomes. Inhibitory protein families such as FLIPs and CARD-only proteins prevent the recruitment of caspases in these sensing complexes, avoiding inappropriate initiation of cell death or inflammation.
authors.affiliation: Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical Research, VIB and Ghent University, Fiers-Schell-Van Montagu Building, Technologiepark 927, B-9052 Ghent, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Festjens
authors.forename: Sigrid
authors.initials: S
authors.lastname: Cornelis
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lamkanfi
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
mesh_terms: D000818:Animals; D020169:Caspases / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D006801:Humans; D007249:Inflammation; D046911:Macromolecular Substances / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D046911:Macromolecular Substances; D020169:Caspases