高等学校化学研究 ›› 2024, Vol. 40 ›› Issue (4): 632-645.doi: 10.1007/s40242-024-4120-7
New Frontiers on Intracellular cGAS Activation: Molecular Mechanisms, Cellular Signaling, and Therapeutic Strategies
SONG Xingrui1,2, LING Xiaoting1, LIU Hailong1, ZHAO Qiang1, LI Xiangjun2, LAI Weiyi1, WANG Hailin1,2
- 1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, P. R. China;
2. School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 101408, P. R. China
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收稿日期:2024-05-11出版日期:2024-08-01发布日期:2024-07-24 -
通讯作者:LAI Weiyi,wylai@rcees.ac.cn E-mail:wylai@rcees.ac.cn -
基金资助:This work was supported by the National Natural Science Foundation of China (Nos. 22274166, 22021003, 22234008, 21927807) and the Project of the Youth Innovation Promotion Association, Chinese Academy of Sciences (No. 2023047).
New Frontiers on Intracellular cGAS Activation: Molecular Mechanisms, Cellular Signaling, and Therapeutic Strategies
SONG Xingrui1,2, LING Xiaoting1, LIU Hailong1, ZHAO Qiang1, LI Xiangjun2, LAI Weiyi1, WANG Hailin1,2
- 1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, P. R. China;
2. School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 101408, P. R. China
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Received:2024-05-11Online:2024-08-01Published:2024-07-24 -
Contact:LAI Weiyi,wylai@rcees.ac.cn E-mail:wylai@rcees.ac.cn -
Supported by:This work was supported by the National Natural Science Foundation of China (Nos. 22274166, 22021003, 22234008, 21927807) and the Project of the Youth Innovation Promotion Association, Chinese Academy of Sciences (No. 2023047).
摘要： Cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a pivotal role in the innate immune system. As the primary DNA sensor in cells, cGAS binds to dsDNA in the cytoplasm and forms cGAS-DNA liquid-liquid phase separation (LLPS) and activates its catalytic activity. This activation triggers the cGAS-stimulator of interferon genes (STING) signaling pathway, establishing an efficient system for pathogen detection. Beyond pathogen surveillance, cGAS performs a diverse range of roles, involved in inflammatory response, metabolic homeostasis, DNA damage repair, and cell death. These biological functions regulate cellular physiological homeostasis and influence the occurrence and development of diseases. This review provides an overview of the structure, localization, and intracellular biological functions of the cGAS-STING signaling pathway and cGAS-DNA LLPS. Furthermore, we discuss their contribution to the development of tumors, autoimmune diseases, and inflammatory diseases and highlight the innovative strategies in modulating cGAS activity, either through activation or inhibition, as a promising therapeutic approach.
引用本文
SONG Xingrui, LING Xiaoting, LIU Hailong, ZHAO Qiang, LI Xiangjun, LAI Weiyi, WANG Hailin. New Frontiers on Intracellular cGAS Activation: Molecular Mechanisms, Cellular Signaling, and Therapeutic Strategies[J]. 高等学校化学研究, 2024, 40(4): 632-645.
SONG Xingrui, LING Xiaoting, LIU Hailong, ZHAO Qiang, LI Xiangjun, LAI Weiyi, WANG Hailin. New Frontiers on Intracellular cGAS Activation: Molecular Mechanisms, Cellular Signaling, and Therapeutic Strategies[J]. Chemical Research in Chinese Universities, 2024, 40(4): 632-645.
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