cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway

Function

• component of the innate immune system
  • detects cytosolic DNA & triggers immune responses
• role in antiviral defense, tumor immunity, & regulation of autophagy & cellular senescence
• cyclic GMP-AMP synthase (cGAS) is a cytosolic enzyme that senses double-stranded DNA (dsDNA) from pathogens or damaged host cells
• upon binding to dsDNA, cGAS catalyzes synthesis of cyclic GMP-AMP from ATP & GTP
• cyclic GMP-AMP acts as a second messenger that binds to & activates the stimulator of interferon genes (STING) protein, located on the endoplasmic reticulum membrane
• upon activation, STING undergoes a conformational change & translocates to the Golgi apparatus, where it recruits & activates TANK-binding kinase 1 (TBK1)
• TBK1 phosphorylates & activates IRF3 & IRF7 & allows their nuclear localization;
• this leads to production of IFN alpha/beta & & other pro-inflammatory cytokines & development of a cellular antiviral state

Pathology

• dysregulation of this pathway can lead to autoimmune & inflammatory diseases due to inappropriate recognition of self-DNA

More general terms

• molecular pathway