Post-Translational Modifications of cGAS-STING: A Critical Switch for Immune Regulation

Innate immune mechanisms initiate immune responses via pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of the PRRs, senses diverse pathogenic or endogenous DNA and activates innate immune signaling pathways, including the expression of stimulator of interferon genes (STING), type I interferon, and other inflammatory cytokines, which, in turn, instructs the adaptive immune response development. This groundbreaking discovery has rapidly advanced research on host defense, cancer biology, and autoimmune disorders. Since cGAS/STING has enormous potential in eliciting an innate immune response, understanding its functional regulation is critical. As the most widespread and efficient regulatory mode of the cGAS-STING pathway, post-translational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are generally considered a regulatory mechanism for protein destruction or renewal. In this review, we discuss cGAS-STING signaling transduction and its mechanism in related diseases and focus on the current different regulatory modalities of PTMs in the control of the cGAS-STING-triggered innate immune and inflammatory responses.

Automated summary

Innate immune mechanisms initiate immune responses through pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of PRRs, senses various pathogenic or endogenous DNA and activates innate immune signaling pathways, regulating the development of adaptive immune response. Post-translational modifications (PTMs) of the cGAS-STING pathway play a crucial role in its functional regulation.