Regulation of cGAS-STING signalling and its diversity of cellular outcomes

Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway, which recognizes both pathogen DNA and host-derived DNA, has emerged as a crucial component of the innate immune system, having important roles in antimicrobial defence, inflammatory disease, ageing, autoimmunity and cancer. Recent work suggests that the regulation of cGAS-STING signalling is complex and sophisticated. In this Review, we describe recent insights from structural studies that have helped to elucidate the molecular mechanisms of the cGAS-STING signalling cascade and we discuss how the cGAS-STING pathway is regulated by both activating and inhibitory factors. Furthermore, we summarize the newly emerging understanding of crosstalk between cGAS-STING signalling and other signalling pathways and provide examples to highlight the wide variety of cellular processes in which cGAS-STING signalling is involved, including autophagy, metabolism, ageing, inflammation and tumorigenesis.