TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral signaling by promoting TBK1 K48 ubiquitination
| Autor: | W. June Brickey, Shao Cong Sun, Beckley K. Davis, Kaixin Liang, Jenny P.-Y. Ting, Lufei Wang, Jason W. Tam, Sirui Li, Yang Zhang, Alex Petrucelli, Haitao Guo, Brian J. Conti, Meng Deng, Ching-Chang Ko, Lu Zhang, Yu Lei, Xiaobo Luo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
TRAF3 THP-1 Cells General Physics and Astronomy Diseases Jurkat cells Jurkat Cells 0302 clinical medicine Cytosol Interferon Chlorocebus aethiops Myeloid Cells lcsh:Science Cells Cultured Innate immunity Mice Knockout Multidisciplinary biology Chemistry Cell biology Vesicular stomatitis virus Interferon Type I Infectious diseases RNA Viral medicine.drug Science Immunology Mice Transgenic Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Article Vesicular stomatitis Indiana virus Cell Line 03 medical and health sciences Immune system medicine Animals Humans Vero Cells Mitochondrial antiviral-signaling protein Innate immune system Lysine Ubiquitination RNA Membrane Proteins General Chemistry biology.organism_classification Mice Inbred C57BL 030104 developmental biology HEK293 Cells Gene Expression Regulation lcsh:Q Carrier Proteins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3−/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells. RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses. |
| Databáze: | OpenAIRE |
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