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. 2021 Apr 30;6:170. doi: 10.1038/s41392-021-00554-y

Fig. 2. The cGAS–STING signaling pathway senses cytosolic DNA derived from either viral/bacterial infection or self-DNA.

Fig. 2

DNA is a pathogen-associated molecular pattern when delivered to the host cytoplasm by viral or microbial infection, and a danger-associated molecular pattern when leaked into the cytoplasm from damaged mitochondria or nucleus. cGAS is the cytosolic DNA sensor that recognizes and binds cytosolic DNA in a DNA-sequence-independent manner that subsequently triggers cGAS dimerization and production of a special dinucleotide messenger, 2′3′-cGAMP from ATP and GTP. 2′3′-cGAMP binds STING localized on ER, through trafficking to Golgi to recruit and activate IKK and TBK1. TBK1 phosphorylates STING, which in turn recruits IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dimerizes and enters the nucleus, where it cooperates with NF-κB signaling to turn on transcription of type I IFNs and other immunomodulatory genes