title: Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death.
abstract: Pyroptosis was long regarded as caspase-1-mediated monocyte death in response to certain bacterial insults. Caspase-1 is activated upon various infectious and immunological challenges through different inflammasomes. The discovery of caspase-11/4/5 function in sensing intracellular lipopolysaccharide expands the spectrum of pyroptosis mediators and also reveals that pyroptosis is not cell type specific. Recent studies identified the pyroptosis executioner, gasdermin D (GSDMD), a substrate of both caspase-1 and caspase-11/4/5. GSDMD represents a large gasdermin family bearing a novel membrane pore-forming activity. Thus, pyroptosis is redefined as gasdermin-mediated programmed necrosis. Gasdermins are associated with various genetic diseases, but their cellular function and mechanism of activation (except for GSDMD) are unknown. The gasdermin family suggests a new area of research on pyroptosis function in immunity, disease, and beyond.
authors.affiliation: National Institute of Biological Sciences, Number 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.
authors.forename: Jianjin
authors.initials: J
authors.lastname: Shi
authors.affiliation: National Institute of Biological Sciences, Number 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.affiliation: National Institute of Biological Sciences, Number 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China. Electronic address: shaofeng@nibs.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009336:Necrosis / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D028044:Phosphate-Binding Proteins; D000069292:Pyroptosis; D000094524:Gasdermins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D028044:Phosphate-Binding Proteins; C498366:GSDMD protein, human; D000094524:Gasdermins
keywords: caspase; gasdermin; innate immunity; necrosis; pore-forming protein; pyroptosis