SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS.

Mitochondrial virus-induced signal adaptor (MAVS), also known as VISA, IPS-1, and Cardif, is a crucial adaptor protein in the RIG-I-like receptor (RLR) signaling pathway. Upon viral infection, RIG-I recognizes viral dsRNA and further transfers it to mitochondria, where it binds to MAVS through its CARD domain, generating a series of ...
signal cascades. Transduction through this signaling cascade leads to phosphorylation and nuclear translocation of interferon regulatory factor 3/7 (IRF3/IRF7) and activation of NF-?B, which ultimately produces type I interferon (IFN) and proinflammatory cytokines. Here, our experiments demonstrated that overexpression of SRY-related high-mobility group protein 9 (SOX9) significantly inhibited Sendai virus (SeV)-induced and MAVS-mediated activation of the IFN-? promoter and ISRE. However, knocking out the expression of SOX9 in cells promoted SeV-induced IFN-? promoter and ISRE activation. Further studies have shown that SOX9 interacts with MAVS and targets MAVS to inhibit the association of MAVS-TRAF2, thereby inhibiting MAVS-mediated TRAF2 ubiquitination. Taken together, these results indicate that SOX9 downregulates IFN-? expression and antiviral signal transduction by targeting MAVS.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antiviral Agents, Mitochondria, SOX9 Transcription Factor, Signal Transduction, Ubiquitination
Virus Genes
Date: Apr. 01, 2022
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