cGAS/STING: novel perspectives of the classic pathway

Menghui Gao; Yuchen He; Haosheng Tang; Xiangyu Chen; Shuang Liu; Yongguang Tao

doi:10.1186/s43556-020-00006-z

cGAS/STING: novel perspectives of the classic pathway

Mol Biomed. 2020 Sep 20;1(1):7. doi: 10.1186/s43556-020-00006-z.

Authors

Menghui Gao^#¹, Yuchen He^#¹, Haosheng Tang^{1

2}, Xiangyu Chen^{1

2}, Shuang Liu³, Yongguang Tao^{4

5

6}

Affiliations

¹ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078, China.
² NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, 410078, Hunan, China.
³ Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. shuangliu2016@csu.edu.cn.
⁴ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078, China. taoyong@csu.edu.cn.
⁵ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, 410078, Hunan, China. taoyong@csu.edu.cn.
⁶ Hunan Key Laboratory of Tumor Models and Individualized Medicine, Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, China. taoyong@csu.edu.cn.

^# Contributed equally.

Abstract

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.

Keywords: DNA sensor; Immune; Micronuclei; Nuclei; STING; Senescence; Tumor; cGAS.

Publication types

Review

Abstract

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