Cytosolic DNA sensing by cGAS:regulation,function,and human diseases  

作　　者：Le Yu Pengda Liu 

机构地区：[1]Lineberger Comprehensive Cancer Center,The University of North Carolina at Chapel Hill,Chapel Hill,NC,USA [2]Department of Biochemistry and Biophysics,The University of North Carolina at Chapel Hill,Chapel Hill,NC,USA

出　　处：《Signal Transduction and Targeted Therapy》2021年第5期1483-1497,共15页信号转导与靶向治疗（英文）

基　　金：We sincerely apologize to all colleagues whose important work could not be cited in this review owing to space limitations,especially many prominent and pioneer work in the cGAS/cGAMP/STING field.This work was supported by an NIH grant(R01CA244825,P.L.);the Breast Cancer Alliance Young Investigator Grant(P.L.);the Gabrielle's Angel Foundation Medical Research Award(P.L.);the UNC University Cancer Research Fund(P.L.).

摘　　要：Sensing invasive cytosolic DNA is an integral component of innate immunity.cGAS was identified in 2013 as the major cytosolic DNA sensor that binds dsDNA to catalyze the synthesis of a special asymmetric cyclic-dinucleotide,2/3/-cGAMP,as the secondary messenger to bind and activate STING for subsequent production of type I interferons and other immune-modulatory genes.Hyperactivation of cGAS signaling contributes to autoimmune diseases but serves as an adjuvant for anticancer immune therapy.On the other hand,inactivation of cGAS signaling causes deficiency to sense and clear the viral and bacterial infection and creates a tumor-prone immune microenvironment to facilitate tumor evasion of immune surveillance.Thus,cGAS activation is tightly controlled.In this review,we summarize up-to-date multilayers of regulatory mechanisms governing cGAS activation,including cGAS pre-and post-translational regulations,cGAS-binding proteins,and additional cGAS regulators such as ions and small molecules.We will also reveal the pathophysiological function of cGAS and its product cGAMP in human diseases.We hope to provide an up-to-date review for recent research advances of cGAS biology and cGAS-targeted therapies for human diseases.

关 键 词：DISEASES FUNCTION cGAS 

分 类 号：R363[医药卫生—病理学]