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    Nuclear Factor κB Subunits RelB and cRel Negatively Regulate Toll-like Receptor 3-mediated β-Interferon Production via Induction of Transcriptional Repressor Protein YY1


    Siednienko, Jackub and Maratha, Ashwini and Yang, Shuo and Mitkiewicz, Malgorzata and Miggin, Sinead and Moynagh, Paul N. (2011) Nuclear Factor κB Subunits RelB and cRel Negatively Regulate Toll-like Receptor 3-mediated β-Interferon Production via Induction of Transcriptional Repressor Protein YY1. Journal of Biological Chemistry, 286 (52). pp. 44750-44763. ISSN 0021-9258

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    Abstract

    The induction of β-interferon (IFN-β) is a key anti-viral response to infection by RNA viruses. Virus-induced expression of IFN-β requires the co-operative action of the transcription factors IRF-3/7, NF-κB, and ATF-2/c-Jun on the IFN-β promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-κB and promote its binding to the IFN-β promoter, recent studies have indicated that NF-κB is not essential for virus-induced expression of IFN-β. Herein, we examined the role of NF-κB in regulating IFN-β expression in response to the viral-sensing Toll-like receptor 3 (TLR3). Intriguingly pharmacological inhibition of the NF-κB pathway augments late phase expression of IFN-β expression in response to TLR3 stimulation. We show that the negative effect of NF-κB on IFN-β expression is dependent on the induction of the transcriptional repressor protein YinYang1. We demonstrate that the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) induces expression and nuclear translocation of YinYang1 where it interacts with the IFN-β promoter and inhibits the binding of IRF7 to the latter. Evidence is also presented showing that the NF-κB subunits c-Rel and RelB are the likely key drivers of these negative effects on IFN-β expression. These findings thus highlight for the first time a novel self-regulatory mechanism that is employed by TLR3 to limit the level and duration of IFN-β expression.

    Item Type: Article
    Keywords: Nuclear Factor κB; RelB; cRel; Negatively Regulate Toll-like Receptor; 3-mediated; β-Interferon; Production via Induction; Transcriptional Repressor Protein YY1;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 9129
    Depositing User: Professor Paul Moynagh
    Date Deposited: 19 Feb 2018 16:53
    Journal or Publication Title: Journal of Biological Chemistry
    Publisher: American Society for Biochemistry and Molecular Biology
    Refereed: Yes
    Funders: Science Foundation Ireland award, Health Research Board of Ireland awards
    URI:

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