Stimulator of Interferon Genes (STING)

The cGAS-STING pathway is a central component of the innate immune system responsible for detecting abnormal cytosolic DNA, typically from viral infection, tumors, or cell damage. cGAS senses double-stranded DNA (dsDNA) in the cytosol and synthesizes the second messenger cGAMP, which binds to and activates STING. Activated STING initiates downstream signaling that leads to the production of type I interferons and pro-inflammatory cytokines. While essential for antimicrobial defense and tumor surveillance, aberrant activation of this pathway is implicated in various autoimmune and inflammatory disorders, cancer, and metabolic diseases. Therapeutically, both inhibition and activation of this pathway are being explored for diverse clinical indications depending on context.

Other names

STINGTMEM173Transmembrane protein 173MPYSERISMITAC6orf150cGAMP receptorFor cGAS: cyclic GMP-AMP synthase

STING agonists bind to and activate STING, causing translocation and conformational change, leading to TBK1 and IRF3 activation and IFN-β/immune gene expression. cGAS inhibitors block dsDNA sensing and prevent cGAMP synthesis, thus halting downstream STING activation. Some agents act upstream (block DNA binding to cGAS) or downstream (modulate IRF3/NF-κB).