Figure 1.

The cytosolic DNA-activated cGAS-STING pathway. The recognition of free dsDNA in the cytoplasm by cGAS activates the production of 2’-3’-cGAMP, a natural ligand of ER-resident STING. The binding of 2’-3’-cGAMP to STING results in its translocation to the ER-Golgi intermediate compartment (ERGIC) and the Golgi apparatus. The relocated STING activates TBK1 and IKK. First, activated TBK1 phosphorylates STING, which consequently recruits and phosphorylates IRF3. The phosphorylated activated IRF3 dimerizes and enters the nucleus to initiate transcription of type I IFN. In addition, activated IKK results in the activation and nuclear transport of NF-κB to induce the expression of type I IFN and inflammatory cytokines such as TNF and IL-6. The interaction between cGAS and nucleosomes prevents the activation of cGAS. Notably, nuclear cGAS suppresses homologous recombination and promotes tumorigenesis.