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MINI REVIEW article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1522200
This article is part of the Research Topic The Role of Ubiquitination in Disease Development, Progression, and Prognosis View all 9 articles

The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases

Provisionally accepted
Chunyan Deng Chunyan Deng 1Dongyan Chen Dongyan Chen 1Liang Yang Liang Yang 2Yubiao Zhang Yubiao Zhang 3Cheng Jin Cheng Jin 1Yue Li Yue Li 1Qihong Lin Qihong Lin 1Mingjing Luo Mingjing Luo 1Ruihao Zheng Ruihao Zheng 1Baozhen Huang Baozhen Huang 4*Si-xi Liu Si-xi Liu 1*
  • 1 Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China
  • 2 Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, Guangdong Province, China
  • 3 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hebei Province, China
  • 4 Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, SAR China

The final, formatted version of the article will be published soon.

    The cGAS-STING pathway is essential in innate immunity, especially in antiviral responses and cellular stress management. cGAS acts as a cytoplasmic DNA sensor by initiating the synthesis of the second messenger cyclic GMP-AMP synthase (cGAMP), which subsequently activates the STING pathway, leading to the production of type I interferons and other cytokines, as well as the activation of inflammatory mediators. Recent studies have demonstrated that ubiquitination changes closely regulate the function of the cGAS-STING pathway. Ubiquitination modifications influence the stability and activity of cGAS and STING, while also influencing the accuracy of the immune response by adjusting their degradation and signal intensity. E3 ubiquitin ligase specifically facilitates the degradation or modulates the signaling of cGAS-STING-associated proteins via ubiquitination alterations. Furthermore, the ubiquitination of the cGAS-STING pathway serves distinct functions in various cell types and engages with NF-κB, IRF3/7, autophagy, and endoplasmic reticulum stress. This ubiquitin-mediated regulation is crucial for sustaining the balance of innate immunity, while excessive or inadequate ubiquitination can result in autoimmune disorders, cancers, and viral infections. An extensive examination of the ubiquitination process within the cGAS-STING

    Keywords: CGAS, STING, Ubiquitination, innate immunity, Cancer

    Received: 04 Nov 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Deng, Chen, Yang, Zhang, Jin, Li, Lin, Luo, Zheng, Huang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Baozhen Huang, Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, SAR China
    Si-xi Liu, Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, 518000, China

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