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.