CGAS-STING signaling pathway and diseases

Abstract

The cGAS-STING pathway plays a significant role in host defense against viral and bacterial infection. In the process, the cytoplasmic free DNA, considered as a danger signal, is recognized by nucleotidyl transferase cGAS. cGAS is activated by double-stranded DNA (dsDNA) and catalyzes the synthesis of a noncanonical cyclic dinucleotide 2'5'-cGAMP from adenosine triphosphate (ATP) and guanosine triphosphate (GTP). cGAMP serve as an endogenous second messenger to stimulate the induction of type I interferons via STING. In addition to the exogenous bacterial or viral DNA, abnormal deposition of host DNA in cytosol also activates the cGAS-STING signaling pathway cascade, resulting in inflammation and autoimmune diseases. Subsequent studies found that this pathway also plays an important role in tumor's responsiveness to radio-therapy and chemo-therapy. Activation of cGAS-STING pathway produces or enhances the therapeutic efficacy. These findings suggest that specifically interfering with cGAS-STING activation may hold therapeutic value for the treatment of cancer, infection and inflammatory diseases. In this paper, the activation mechanism of cGAS-STING pathway and its relationship with the treatment of diseases were summarized, and the regulation of cGAS-STING pathway was introduced in detail. Key words: cGAS-STING pathway; Regulation; Tumor therapy; Autoimmune disease