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Review
. 2025 Jun;25(6):425-444.
doi: 10.1038/s41577-024-01112-7. Epub 2025 Jan 7.

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

Zhengyin Zhang  1 , Conggang Zhang  2   3
Affiliations
Review

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

Zhengyin Zhang et al. Nat Rev Immunol. 2025 Jun.

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.

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Conflict of interest statement

Competing interests: C.Z. has filed a patent application entitled “Function and application of SMPDL3A as a cGAMP-degrading enzyme”. Z.Z. declares no competing interests.

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