Autor: |
Tian-Sheng He, Tao Xie, Jing Li, Ya-Xian Yang, Changsheng Li, Weiying Wang, Lingzhen Cao, Hua Rao, Cynthia Ju, Liang-Guo Xu |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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Zdroj: |
Viruses, Vol 11, Iss 2, p 158 (2019) |
Druh dokumentu: |
article |
ISSN: |
1999-4915 |
DOI: |
10.3390/v11020158 |
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)-κB 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-β 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: |
Directory of Open Access Journals |
Externí odkaz: |
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