Cytosolic DNA sensing by cGAS:regulation,function,and human diseases
作者机构：Lineberger Comprehensive Cancer CenterThe University of North Carolina at Chapel HillChapel HillNCUSA Department of Biochemistry and BiophysicsThe University of North Carolina at Chapel HillChapel HillNCUSA
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第5期
页 面：1483-1497页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学]
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.
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