THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1
| Autor: | Liang-Guo Xu, Tao Xie, Jing Li, Tian-sheng He, Cynthia Ju, Changsheng Li, Hua Rao, Ya-Xian Yang, Lingzhen Cao, Weiying Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex THO complex TBK1 cellular antiviral response lcsh:QR1-502 Protein Serine-Threonine Kinases Sendai virus Article lcsh:Microbiology 03 medical and health sciences 0302 clinical medicine TANK-binding kinase 1 Virology Humans Phosphorylation Transcription factor Immunity Cellular biology Ubiquitin Chemistry Ubiquitination RNA-Binding Proteins MAVS signalosome THOC7 biology.organism_classification Immunity Innate Cell biology HEK293 Cells 030104 developmental biology Infectious Diseases Gene Expression Regulation 030220 oncology & carcinogenesis Interferon Type I MCF-7 Cells Interferon Regulatory Factor-3 Signal transduction IRF3 Protein Binding Signal Transduction Interferon regulatory factors |
| Zdroj: | Viruses, Vol 11, Iss 2, p 158 (2019) Viruses Volume 11 Issue 2 |
| ISSN: | 1999-4915 |
| Popis: | RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase 1 (TBK1) is recruited to the MAVS signalosome to transduce a robust innate antiviral immune response by phosphorylating transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-&kappa B and promoting their nuclear translocation. However, the molecular mechanisms underlying the negative regulation of TBK1 are largely unknown. In the present study, we found that THO complex subunit 7 homolog (THOC7) negatively regulated the cellular antiviral response by promoting the proteasomal degradation of TBK1. THOC7 overexpression potently inhibited Sendai virus- or polyI:C-induced IRF3 dimerization and phosphorylation and IFN-&beta production. In contrast, THOC7 knockdown had the opposite effects. Moreover, we simulated a node-activated pathway to show that THOC7 regulated the RIG-I-like receptors (RLR)-/MAVS-dependent signaling cascade at the TBK1 level. Furthermore, THOC7 was involved in the MAVS signalosome and promoted TBK1 degradation by increasing its K48 ubiquitin-associated polyubiquitination. Together, these findings suggest that THOC7 negatively regulates type I IFN production by promoting TBK1 proteasomal degradation, thus improving our understanding of innate antiviral immune responses. |
| Databáze: | OpenAIRE |
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