Sun Zhiqi, Hornung Veit
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany; Max-Planck Institute of Biochemistry, Martinsried, Germany.
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany; Max-Planck Institute of Biochemistry, Martinsried, Germany.
Curr Biol. 2022 Jul 11;32(13):R730-R734. doi: 10.1016/j.cub.2022.05.027.
Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING, also known as TMEM173) constitute the major signaling pathway in vertebrates that senses non-self DNA and elicits potent immune responses. At the core of this pathway, cGAS senses double-stranded DNA (dsDNA) and synthesizes cyclic GMP-AMP (cGAMP). cGAMP serves as a second messenger that relays its signal to downstream innate immune responses through STING. One of the major consequences triggered by the cGAS-STING pathway is the production of antiviral cytokines of the type I interferon family, which in turn induce expression of hundreds of interferon-stimulated genes (ISGs) with diverse antiviral functions. Recent studies have also revealed functional homologs across phylogenetic kingdoms with innate defense functions, suggesting an ancient evolutionary origin of cGAS-STING signaling. Aberrant activation of the cGAS-STING pathway by host DNA can lead to sterile inflammation associated with tissue damage, degeneration as well as premature aging. In this primer, we will introduce the basic principles of cGAS-STING signaling in the vertebrate system and highlight recent discoveries regarding its connection to other fundamental cellular processes in the context of human diseases.
环鸟苷酸-腺苷酸合成酶（cGAS）和干扰素基因刺激因子（STING，也称为TMEM173）构成了脊椎动物中感应非自身DNA并引发强烈免疫反应的主要信号通路。在该通路的核心，cGAS感应双链DNA（dsDNA）并合成环鸟苷酸-腺苷酸（cGAMP）。cGAMP作为第二信使，通过STING将其信号传递至下游先天性免疫反应。cGAS-STING通路引发的主要后果之一是I型干扰素家族抗病毒细胞因子的产生，这些细胞因子进而诱导数百种具有不同抗病毒功能的干扰素刺激基因（ISG）的表达。最近的研究还揭示了不同进化分支中具有先天性防御功能的功能同源物，这表明cGAS-STING信号通路具有古老的进化起源。宿主DNA对cGAS-STING通路的异常激活可导致与组织损伤、退化以及早衰相关的无菌性炎症。在本入门介绍中，我们将介绍脊椎动物系统中cGAS-STING信号传导的基本原理，并重点介绍在人类疾病背景下其与其他基本细胞过程之间联系的最新发现。
