Gao Menghui, He Yuchen, Tang Haosheng, Chen Xiangyu, Liu Shuang, Tao Yongguang
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078, China.
NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, 410078, Hunan, China.
Mol Biomed. 2020 Sep 20;1(1):7. doi: 10.1186/s43556-020-00006-z.
Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor and innate immune response initiator. Binding with exogenous or endogenous nucleic acids, cGAS activates its downstream adaptor, stimulator of interferon genes (STING). STING then triggers protective immune to enable the elimination of the pathogens and the clearance of cancerous cells. Apparently, aberrantly activated by self-DNA, cGAS/STING pathway is threatening to cause autoimmune and inflammatory diseases. The effects of cGAS/STING in defenses against infection and autoimmune diseases have been well studied, still it is worthwhile to discuss the roles of cGAS/STING pathway beyond the "classical" realm of innate immunity. Recent studies have revealed its involvement in non-canonical inflammasome formation, calcium hemostasis regulation, endoplasmic reticulum (ER) stress response, perception of leaking mitochondrial DNA (mtDNA), autophagy induction, cellular senescence and senescence-associated secretory phenotype (SASP) production, providing an exciting area for future exploration. Previous studies generally focused on the function of cGAS/STING pathway in cytoplasm and immune response. In this review, we summarize the latest research of this pathway on the regulation of other physiological process and STING independent reactions to DNA in micronuclei and nuclei. Together, these studies provide a new perspective of cGAS/STING pathway in human diseases.
环磷酸鸟苷-腺苷酸（cGAMP）合酶（cGAS）是一种胞质DNA传感器和先天性免疫反应启动子。与外源性或内源性核酸结合后，cGAS激活其下游衔接蛋白——干扰素基因刺激因子（STING）。STING随后触发保护性免疫反应，以清除病原体和癌细胞。显然，cGAS/STING通路被自身DNA异常激活后，有引发自身免疫性疾病和炎症性疾病的风险。cGAS/STING在抗感染和自身免疫性疾病防御中的作用已得到充分研究，但仍值得探讨cGAS/STING通路在先天性免疫“经典”领域之外的作用。最近的研究表明，它参与非经典炎性小体形成、钙稳态调节、内质网（ER）应激反应、对泄漏线粒体DNA（mtDNA）的感知、自噬诱导、细胞衰老以及衰老相关分泌表型（SASP）的产生，为未来探索提供了一个令人兴奋的领域。以往的研究通常集中在cGAS/STING通路在细胞质和免疫反应中的功能。在这篇综述中，我们总结了该通路在调节其他生理过程以及STING对微核和细胞核中DNA的独立反应方面的最新研究。总之，这些研究为cGAS/STING通路在人类疾病中的作用提供了新的视角。
