THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1.

摘要: 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 rapid production type I interferons (IFNs) proinflammatory cytokines. During this process, pivotal kinase TANK binding 1 (TBK1) is recruited to MAVS transduce robust innate antiviral immune response phosphorylating transcription factors interferon regulatory factor 3 (IRF3) nuclear (NF)-κB their translocation. However, molecular mechanisms underlying negative regulation TBK1 are largely unknown. In present study, we found that THO complex subunit 7 homolog (THOC7) negatively regulated cellular proteasomal degradation TBK1. THOC7 overexpression potently inhibited Sendai virus- or polyI:C-induced IRF3 dimerization phosphorylation IFN-β production. contrast, knockdown had opposite effects. Moreover, simulated node-activated show receptors (RLR)-/MAVS-dependent cascade at level. Furthermore, was involved in promoted increasing its K48 ubiquitin-associated polyubiquitination. Together, these findings suggest regulates IFN degradation, thus improving our understanding responses.