首页|New Frontiers on Intracellular cGAS Activation:Molecular Mechanisms,Cellular Signaling,and Therapeutic Strategies

New Frontiers on Intracellular cGAS Activation:Molecular Mechanisms,Cellular Signaling,and Therapeutic Strategies

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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.

Cyclic GMP-AMP(cGAMP)synthase(cGAS)-stimulator of interferon genes(cGAS-STING)Liquid-liquid phase separation(LLPS)Biological functionDisease

SONG Xingrui、LING Xiaoting、LIU Hailong、ZHAO Qiang、LI Xiangjun、LAI Weiyi、WANG Hailin

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State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 10085,P.R.China

School of Chemical Sciences,University of Chinese Academy of Sciences,Beijing 101408,P.R.China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaProject of the Youth Innovation Promotion Association,Chinese Academy of Sciences

222741662202100322234008219278072023047

2024

10.1007/s40242-024-4120-7

高等学校化学研究(英文版)
吉林大学

高等学校化学研究(英文版)

CSTPCD
影响因子：0.871
ISSN：1005-9040
年,卷(期)：2024.40(4)