Regulation of cGAS and STING signaling during inflammation and infection

J Biol Chem. 2023 Jul;299(7):104866. doi: 10.1016/j.jbc.2023.104866. Epub 2023 May 27.

Abstract

Stimulator of interferon genes (STING) is a sensor of cyclic dinucleotides including cyclic GMP-AMP, which is produced by cyclic GMP-AMP synthase (cGAS) in response to cytosolic DNA. The cGAS-STING signaling pathway regulates both innate and adaptive immune responses, as well as fundamental cellular functions such as autophagy, senescence, and apoptosis. Mutations leading to constitutive activation of STING cause devastating human diseases. Thus, the cGAS-STING pathway is of great interest because of its role in diverse cellular processes and because of the potential therapeutic implications of targeting cGAS and STING. Here, we review molecular and cellular mechanisms of STING signaling, and we propose a framework for understanding the immunological and other cellular functions of STING in the context of disease.

Keywords: COPA syndrome; SAVI; STING; STING-associated vasculopathy with onset in infancy; autoimmunity; autoinflammation; autophagy; cGAS; interferon; signaling.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytosol / metabolism
  • DNA / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / metabolism
  • Nucleotidyltransferases* / genetics
  • Nucleotidyltransferases* / metabolism
  • Signal Transduction* / physiology

Substances

  • Nucleotidyltransferases
  • DNA