Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Immunity. 2020 Jul 14;53(1):43-53. doi: 10.1016/j.immuni.2020.05.013.
Besides its role as the blueprint of life, DNA can also alert the cell to the presence of microbial pathogens as well as damaged or malignant cells. A major sensor of DNA that triggers the innate immune response is cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP activates stimulator of interferon genes (STING), which activates a signaling cascade leading to the production of type I interferons and other immune mediators. Recent research has demonstrated an expanding role of the cGAS-cGAMP-STING pathway in many physiological and pathological processes, including host defense against microbial infections, anti-tumor immunity, cellular senescence, autophagy, and autoimmune and inflammatory diseases. Biochemical and structural studies have elucidated the mechanism of signal transduction in the cGAS pathway at the atomic resolution. This review focuses on the structural and mechanistic insights into the roles of cGAS and STING in immunity and diseases revealed by these recent studies.
除了作为生命蓝图的作用外，DNA 还可以提醒细胞注意微生物病原体以及受损或恶性细胞的存在。一种主要的 DNA 传感器，即环鸟苷酸-腺苷酸（cGAMP）合酶（cGAS），可以触发先天免疫反应，该酶可以产生第二信使 cGAMP。cGAMP 激活干扰素基因刺激物（STING），后者激活信号级联反应，导致 I 型干扰素和其他免疫介质的产生。最近的研究表明，cGAS-cGAMP-STING 途径在许多生理和病理过程中具有广泛的作用，包括宿主抵御微生物感染、抗肿瘤免疫、细胞衰老、自噬以及自身免疫和炎症性疾病。生化和结构研究已经阐明了 cGAS 途径中信号转导的机制，达到了原子分辨率。本综述重点介绍了这些最近的研究揭示的 cGAS 和 STING 在免疫和疾病中的作用的结构和机制见解。
