Phase separation in cGAS-STING signaling

Abstract

Biomolecular condensates formed by phase separation are widespread and play critical roles in many physiological and pathological processes. cGAS-STING signaling functions to detect aberrant DNA signals to initiate anti-infection defense and antitumor immunity. At the same time, cGAS-STING signaling must be carefully regulated to maintain immune homeostasis. Interestingly, exciting recent studies have reported that biomolecular phase separation exists and plays important roles in different steps of cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. In addition, several intracellular and extracellular factors have been proposed to modulate the condensates in cGAS-STING signaling. These studies reveal novel activation and regulation mechanisms of cGAS-STING signaling and provide new opportunities for drug discovery. Here, we summarize recent advances in the phase separation of cGAS-STING signaling and the development of potential drugs targeting these innate immune condensates.

Keywords

biomolecular condensates / phase separation / cGAS-STING pathway / cGAS / STING / cGAMP / interferon

References

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Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (No. 32130057), Beijing Natural Science Foundation (No. Z220018), National Key R&D Program of China (Nos. 2018YFA0507203 and 2018YFA0508000), CAS Project for Young Scientists in Basic Research (No. YSBR-074), Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB37030203).

Compliance with ethics guidelines

Conflicts of interest Quanjin Li and Pu Gao declare that they have no conflict of interest.

This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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