TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7
| Autor: | Guang-Xiu Weng, Hua Rao, Changsheng Li, Cynthia Ju, Lingzhen Cao, Jing Li, Ting Ling, Liang-Guo Xu, Weiying Wang |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Molecular immunology. 109 |
| ISSN: | 1872-9142 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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