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Apoptosome and inflammasome: conserved machineries for caspase activation
Abstract:Apoptosome and inlammasome are multimeric protein complexes that mediate the activation of speciic caspases at the onset of apoptosis and inlammation.he central component of apoptosome or inlammasome is a tripartite scafold protein,exempliied by Apaf-1 and NLRC4,which contains an amino-terminal homotypic interaction motif,a central nucleotide-binding oligomerization domain and a carboxyl-terminal ligand-sensing domain.In the absence of death cue or an inlammatory signal,Apaf-1 or NLRC4 exists in an auto-inhibited,monomeric state,which is stabilized by adenosine diphosphate(ADP).Binding to an apoptosis-or inlammation-inducing ligand,together with replacement of ADP by adenosine triphosphate(ATP),results in the formation of a multimeric apoptosome or inlammasome.he assembled apoptosome and inlammasome serve as dedicated machineries to facilitate the activation of speciic caspases.In this review,we describe the structure and functional mechanisms of mammalian inlammasome and apoptosomes from three representative organisms.Emphasis is placed on the molecular mechanism of caspase activation and the shared features of apoptosomes and inlammasomes.
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