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Immune Response
Metazoans
cGAS-STING Pathway
Cytosolic DNA sensing pathway activating innate immune defense.
Overview
cGAS (cyclic GMP-AMP synthase) is a cytosolic DNA sensor that detects double-stranded DNA from pathogens, damaged mitochondria, or micronuclei. Upon DNA binding, cGAS synthesizes 2'3'-cGAMP, which binds and activates STING on the ER membrane. STING recruits TBK1, which phosphorylates IRF3, driving type I interferon production and NF-κB activation.
Cellular Location
Cytoplasm, ER
Clinical Significance
Links DNA damage to immunity; activated by tumor-derived DNA; STING agonists in cancer immunotherapy trials; STING gain-of-function causes SAVI (autoinflammatory disease).