Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases

作     者：Jing Pan Chen-Jie Fei Yang Hu Xiang-Yu Wu Li Nie Jiong Chen Jing Pan;Chen-Jie Fei;Yang Hu;Xiang-Yu Wu;Li Nie;Jiong Chen

作者机构：State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-productsNingbo UniversityNingboZhejiang 315211China Laboratory of Biochemistry and Molecular BiologySchool of Marine SciencesMeishan CampusNingbo UniversityNingboZhejiang 315832China Zhejiang Key Laboratory of Marine BioengineeringNingbo UniversityNingboZhejiang 315832China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2023年第44卷第1期

页      面：183-218页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071005[理学-微生物学] 

基　　金：supported by the Natural Science Foundation of Zhejiang Province(LY23C190002) National Natural Science Foundation of China(32173004) Natural Science Foundation of Ningbo City(202003N4011)。 

主　　题：cGAS STING Structure Signaling Post-translational modification Diseases 

摘      要：The innate immune system protects the host from external pathogens and internal damage in various ways. The cGAS-STING signaling pathway,comprised of cyclic GMP-AMP synthase(cGAS),stimulator of interferon genes(STING), and downstream signaling adaptors, plays an essential role in protective immune defense against microbial DNA and internal damaged-associated DNA and is responsible for various immune-related diseases.After binding with DNA, cytosolic cGAS undergoes conformational change and DNA-linked liquid-liquid phase separation to produce 2’3’-c GAMP for the activation of endoplasmic reticulum(ER)-localized STING. However, further studies revealed that cGAS is predominantly expressed in the nucleus and strictly tethered to chromatin to prevent binding with nuclear DNA, and functions differently from cytosoliclocalized cGAS. Detailed delineation of this pathway,including its structure, signaling, and regulatory mechanisms, is of great significance to fully understand the diversity of cGAS-STING activation and signaling and will be of benefit for the treatment of inflammatory diseases and cancer. Here, we review recent progress on the above-mentioned perspectives of the cGAS-STING signaling pathway and discuss new avenues for further study.