Opinion
Shedding Light on The cGAS-STING Pathway: A New Tale of An Old Story in The Cell
Qixia Xu1,*, Chen Yang2,*, and Yu Sun1,2,3,✉
1Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 2CAS Key Laboratory of Tissue Microenvironment and Tumor Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; 3Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98195, USA.
* These authors contributed equally. ✉ Correspondence Yu Sun, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Life Sciences Building A-1526, Shanghai, P. R. China 200031. Phone: +86-21-54923302; Fax: +86-21-54923302; Email: [email protected]. Received: July 9, 2020. Accepted: September 14, 2020. Published online: November 20, 2020. Cite this paper: Qixia Xu, Chen Yang and Yu Sun (2020) Shedding light on the cGAS-STING pathway: a new tale of an old story in the cell. Global Journal of Immunology, 1(1): 17-26. https://naturescholars.com/gji.010104. https://doi.org/10.46633/gji.010104. Copyright © 2020 by Scholars Publishing, LLC.
Abstract
Perception of microbial DNA is an evolutionarily conserved defending mechanism that alerts the host immune system to respond to sporadic pathogenic infections, although distinguishing foreign DNA from abundant self-DNA remains a major challenge to host cells. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a central DNA sensor that provokes the innate immunity via production of the second messenger cyclic GMP-AMP (cGAMP), which subsequently engages the stimulator of interferon gene (STING), an adaptor protein. Recent studies uncovered that cytoplasmic chromatin triggers inflammation through surveillance of micronuclei by the cGAS-STING pathway, a process linking genome instability to innate immune responses. Importantly, several lines of emerging evidence suggest that activation of cGAS-STING induces cellular senescence, which is accompanied by the development of a senescent-associated secretory phenotype (SASP), a hallmark feature of senescent cells. Indeed, there are mechanisms intimately associated with genomic DNA damage, cytosol inflammation and cellular senescence, critical events that can determine cell fate but are bridged by enhanced cGAS-STING activities in genotoxic conditions or upon carcinogenic events. Despite the presence of a few unsolved issues, translation of the rapidly accumulated data and development of avenues to target the cGAS-STING pathway may present new options for clinical intervention of auto-inflammation, cellular senescence and age-related pathologies.
Key words: cGAS-STING, Cytosol Sensor, Genomic DNA, Innate Immunity, Cellular Senescence, Senescence-Associated Secretory Phenotype, Targeted Therapy.