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IRTKS negatively regulates antiviral immunity through PCBP2 sumoylation-mediated MAVS degradation

Author

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  • Pengyan Xia

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences)

  • Shuo Wang

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences)

  • Zhen Xiong

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Buqing Ye

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences)

  • Li-Yu Huang

    (Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University
    Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai)

  • Ze-Guang Han

    (Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University
    Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai)

  • Zusen Fan

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

RNA virus infection is recognized by the RIG-I family of receptors that activate the mitochondrial adaptor MAVS, leading to the clearance of viruses. Antiviral signalling activation requires strict modulation to avoid damage to the host from exacerbated inflammation. Insulin receptor tyrosine kinase substrate (IRTKS) participates in actin bundling and insulin signalling and its deficiency causes insulin resistance. However, whether IRTKS is involved in the regulation of innate immunity remains elusive. Here we show that IRTKS deficiency causes enhanced innate immune responses against RNA viruses. IRTKS-mediated suppression of antiviral responses depends on the RIG-I-MAVS signalling pathway. IRTKS recruits the E2 ligase Ubc9 to sumoylate PCBP2 in the nucleus, which causes its cytoplasmic translocation during viral infection. The sumoylated PCBP2 associates with MAVS to initiate its degradation, leading to downregulation of antiviral responses. Thus, IRTKS functions as a negative modulator of excessive inflammation.

Suggested Citation

  • Pengyan Xia & Shuo Wang & Zhen Xiong & Buqing Ye & Li-Yu Huang & Ze-Guang Han & Zusen Fan, 2015. "IRTKS negatively regulates antiviral immunity through PCBP2 sumoylation-mediated MAVS degradation," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9132
    DOI: 10.1038/ncomms9132
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    Cited by:

    1. Haiyan Gu & Jing Yang & Jiayu Zhang & Ying Song & Yao Zhang & Pengfei Xu & Yuanxiang Zhu & Liangliang Wang & Pengfei Zhang & Lin Li & Dahua Chen & Qinmiao Sun, 2022. "PCBP2 maintains antiviral signaling homeostasis by regulating cGAS enzymatic activity via antagonizing its condensation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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