Volume 44 Issue 1
Jan.  2023
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Jing Pan, Chen-Jie Fei, Yang Hu, Xiang-Yu Wu, Li Nie, Jiong Chen. Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases. Zoological Research, 2023, 44(1): 183-218. doi: 10.24272/j.issn.2095-8137.2022.464
Citation: Jing Pan, Chen-Jie Fei, Yang Hu, Xiang-Yu Wu, Li Nie, Jiong Chen. Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases. Zoological Research, 2023, 44(1): 183-218. doi: 10.24272/j.issn.2095-8137.2022.464

Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases

doi: 10.24272/j.issn.2095-8137.2022.464
The authors declare that they have no competing interests.
J.P., C.J.F., and L.N. wrote the original draft, J.P., Y.H., and X.Y.W. drew the figures, Y.H. constructed the tables, and J.C. supervised the project and wrote and edited the manuscript. All authors read and approved the final version of the manuscript.
Funds:  This work was supported by the Natural Science Foundation of Zhejiang Province (LY23C190002), National Natural Science Foundation of China (32173004), and Natural Science Foundation of Ningbo City (202003N4011)
More Information
  • The innate immune system protects the host from external pathogens and internal damage in various ways. The cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and downstream signaling adaptors, plays an essential role in protective immune defense against microbial DNA and internal damaged-associated DNA and is responsible for various immune-related diseases. After binding with DNA, cytosolic cGAS undergoes conformational change and DNA-linked liquid-liquid phase separation to produce 2'3'-cGAMP for the activation of endoplasmic reticulum (ER)-localized STING. However, further studies revealed that cGAS is predominantly expressed in the nucleus and strictly tethered to chromatin to prevent binding with nuclear DNA, and functions differently from cytosolic-localized cGAS. Detailed delineation of this pathway, including its structure, signaling, and regulatory mechanisms, is of great significance to fully understand the diversity of cGAS-STING activation and signaling and will be of benefit for the treatment of inflammatory diseases and cancer. Here, we review recent progress on the above-mentioned perspectives of the cGAS-STING signaling pathway and discuss new avenues for further study.
  • The authors declare that they have no competing interests.
    J.P., C.J.F., and L.N. wrote the original draft, J.P., Y.H., and X.Y.W. drew the figures, Y.H. constructed the tables, and J.C. supervised the project and wrote and edited the manuscript. All authors read and approved the final version of the manuscript.
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