Caspases in Cell Death, Inflammation, and Pyroptosis

Annu Rev Immunol. 2020 Apr 26;38:567-595. doi: 10.1146/annurev-immunol-073119-095439. Epub 2020 Feb 4.

Abstract

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D-induced pyroptosis.

Keywords: PANoptosis; gasdermin; inflammasome; inflammatory caspase; innate immunity; pyroptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers
  • Caspases / genetics
  • Caspases / metabolism*
  • Cell Death* / genetics
  • Disease Susceptibility
  • Enzyme Activation
  • Humans
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Pyroptosis / genetics*
  • Signal Transduction

Substances

  • Biomarkers
  • GSDMA protein, human
  • Neoplasm Proteins
  • Caspases