1. TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7
- Author
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Guang-Xiu Weng, Hua Rao, Changsheng Li, Cynthia Ju, Lingzhen Cao, Jing Li, Ting Ling, Liang-Guo Xu, and Weiying Wang
- Subjects
0301 basic medicine ,Interferon Regulatory Factor-7 ,Immunology ,Regulator ,Sendai virus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Humans ,Phosphorylation ,Molecular Biology ,TNF Receptor-Associated Factor 6 ,Innate immune system ,biology ,Chemistry ,Lysine ,Ubiquitination ,RNA-Binding Proteins ,Interferon-beta ,biology.organism_classification ,Cell biology ,030104 developmental biology ,HEK293 Cells ,Proteolysis ,IRF7 ,Signal transduction ,030215 immunology ,Interferon regulatory factors ,Protein Binding ,Signal Transduction - Abstract
Interferon regulatory factor 7 (IRF7), a crucial regulator of type I interferons (IFNs), plays a crucial role in resistance to viral infection. The abnormal production of type I IFNs is associated with many types of disease, such as cancer and inflammatory disorders. Thus, understanding the post-translational modifications of IRF7 is essential to promoting an appropriate immune response. We have recently showed that the TAR RNA binding protein 2 (TARBP2) suppresses IFN-β production and the innate antiviral response by targeting MAVS. Here, we further identified TARBP2 as a novel inhibitor of IRF7, which inhibits IRF7-mediated IFN-β production triggered by the Sendai virus in 293 T cells. Overexpression of TARBP2 inhibits the phosphorylation as well as the K63-linked ubiquitination of IRF7, whilst TARBP2 also impairs the stability of endogenous TRAF6. Furthermore, TARBP2 participates in the interaction between IRF7 and TRAF6, thereby suppressing TRAF6-mediated K63-linked ubiquitination of IRF7, which is a prerequisite of IRF7 phosphorylation. Our findings further reveal the mechanism by which TARBP2 regulates the antiviral signaling pathways of the innate immune system.
- Published
- 2018