Figure 1.

Mechanism of activation of the cGAS–STING cytosolic DNA sensing pathway. Double-stranded DNA, RNA, and RNA–DNA hybrids from exogenous and endogenous sources are sensed by cGAS. After dsDNA/dsRNA binding on cGAS, cGAS utilizes ATP and GTP to synthesize cGAMP. cGAMP binds to STING at the ER. Upon cGAMP binding, STING traffics from the ER to the Golgi apparatus and finally interact with TBK1 and IRF3 and NF-κB, culminating in IFN-I and pro-inflammatory cytokines production. In addition, aside cGAMP, ER stress can initiate STING activation, leading to IFN-I and pro-inflammatory cytokines production.