期刊
NATIONAL SCIENCE REVIEW
卷 1, 期 1, 页码 101-118出版社
OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwt025
关键词
apoptosome; inflammasome; caspase activation; apoptosis; inflammation
资金
- National Natural Science Foundation of China
- Ministry of Science and Technology of China
Apoptosome and inflammasome are multimeric protein complexes that mediate the activation of specific caspases at the onset of apoptosis and inflammation. The central component of apoptosome or inflammasome is a tripartite scaffold protein, exemplified 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 inflammatory signal, Apaf-1 or NLRC4 exists in an auto-inhibited, monomeric state, which is stabilized by adenosine diphosphate (ADP). Binding to an apoptosis-or inflammation-inducing ligand, together with replacement of ADP by adenosine triphosphate (ATP), results in the formation of a multimeric apoptosome or inflammasome. The assembled apoptosome and inflammasome serve as dedicated machineries to facilitate the activation of specific caspases. In this review, we describe the structure and functional mechanisms of mammalian inflammasome and apoptosomes from three representative organisms. Emphasis is placed on the molecular mechanism of caspase activation and the shared features of apoptosomes and inflammasomes.
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