HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination Recruiting OTUB1

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Innate immunity is critical for the host to defeat pathogen invasion, and the production of interferon (IFN) is the core of the cellular antiviral response, this is mediated by the Toll-like receptor (TLR) and RIG-I like receptor (RLR) signaling pathways in most cell types. As aberrant activity of the immune response leads to immune-deficiency or autoimmune disease, identification of the regulators involved in immune balance is particularly important. Accumulating evidence shows that ubiquitination plays a key role in regulating virus-triggered IFN production to assure that the antiviral response is modulated properly. Here, we demonstrated that HSCARG is a novel negative regulator in the precise control of antiviral innate immunity. HSCARG inhibited IFN-β production by suppressing TRAF3 ubiquitination with the help of OTUB1, leading to disassociation of downstream IKKε and impairment of IRF3 activity. As the pivot of the TLR, RLR, and non-canonical NF-κB pathways, TRAF3 is an extremely versatile immune regulator. Our study sheds light on the mechanism of specificity and diversity achievement in the complicated regulation of TRAF3 activity, suggesting that HSCARG is a potential target for the treatment of inflammatory and autoimmune diseases.

Vyšlo v časopise: HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination Recruiting OTUB1. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004041
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004041

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