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Volume 38 Issue 3
June 2023
    Citation: Jing-Ping Huang, Ya-Xian Yang, Tian Chen, Dan-Dan Wang, Jing Li, Liang-Guo Xu. TRAF7 negatively regulates the RLR signaling pathway by facilitating the K48-linked ubiquitination of TBK1 .VIROLOGICA SINICA, 2023, 38(3) : 419-428.  http://dx.doi.org/10.1016/j.virs.2023.04.005
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    TRAF7 negatively regulates the RLR signaling pathway by facilitating the K48-linked ubiquitination of TBK1

    • College of Life Science, Jiangxi Normal University, Nanchang, 330022, China

    • Corresponding author: Liang-Guo Xu, xul@jxnu.edu.cn
    • Received Date: 10 December 2022
      Accepted Date: 17 April 2023
      Available online: 21 April 2023
    • TANK-binding kinase 1 (TBK1) is a nodal protein involved in multiple signal transduction pathways. In RNA virus-mediated innate immunity, TBK1 is recruited to the prion-like platform formed by MAVS and subsequently activates the transcription factors IRF3/7 and NF-κB to produce type I interferon (IFN) and proinflammatory cytokines for the signaling cascade. In this study, TRAF7 was identified as a negative regulator of innate immune signaling. TRAF7 interacts with TBK1 and promotes K48-linked polyubiquitination and degradation of TBK1 through its RING domain, impairing the activation of IRF3 and the production of IFN-β. In addition, we found that the conserved cysteine residues at position 131 of TRAF7 are necessary for its function toward TBK1. Knockout of TRAF7 could facilitate the activation of IRF3 and increase the transcript levels of downstream antiviral genes. These data suggest that TRAF7 negatively regulates innate antiviral immunity by promoting the K48-linked ubiquitination of TBK1.
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      TRAF7 negatively regulates the RLR signaling pathway by facilitating the K48-linked ubiquitination of TBK1

        Corresponding author: Liang-Guo Xu, xul@jxnu.edu.cn
      • College of Life Science, Jiangxi Normal University, Nanchang, 330022, China
      • Received Date: 10 December 2022
      • Accepted Date: 17 April 2023

      Abstract: TANK-binding kinase 1 (TBK1) is a nodal protein involved in multiple signal transduction pathways. In RNA virus-mediated innate immunity, TBK1 is recruited to the prion-like platform formed by MAVS and subsequently activates the transcription factors IRF3/7 and NF-κB to produce type I interferon (IFN) and proinflammatory cytokines for the signaling cascade. In this study, TRAF7 was identified as a negative regulator of innate immune signaling. TRAF7 interacts with TBK1 and promotes K48-linked polyubiquitination and degradation of TBK1 through its RING domain, impairing the activation of IRF3 and the production of IFN-β. In addition, we found that the conserved cysteine residues at position 131 of TRAF7 are necessary for its function toward TBK1. Knockout of TRAF7 could facilitate the activation of IRF3 and increase the transcript levels of downstream antiviral genes. These data suggest that TRAF7 negatively regulates innate antiviral immunity by promoting the K48-linked ubiquitination of TBK1.

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