Zhang Zhengyin, Zhang Conggang
School of Pharmaceutical Sciences, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.
SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.
Nat Rev Immunol. 2025 Jan 7. doi: 10.1038/s41577-024-01112-7.
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.
环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路可识别病原体DNA和宿主来源的DNA，已成为先天免疫系统的关键组成部分，在抗菌防御、炎症性疾病、衰老、自身免疫和癌症中发挥重要作用。最近的研究表明，cGAS-STING信号通路的调控复杂而精细。在本综述中，我们描述了结构研究的最新见解，这些见解有助于阐明cGAS-STING信号级联反应的分子机制，并讨论cGAS-STING通路是如何受到激活因子和抑制因子的调控。此外，我们总结了对cGAS-STING信号通路与其他信号通路之间相互作用的新认识，并举例说明cGAS-STING信号通路参与的多种细胞过程，包括自噬、代谢、衰老、炎症和肿瘤发生。
