Pellino1 Is Required for Interferon Production by Viral Double-stranded RNA

Karine Enesa, Alban Ordureau, Hilary Smith, David Barford, Peter C. F. Cheung, Janet Patterson-Kane, J Simon C Arthur, Philip Cohen

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    Abstract

    Viral double-stranded RNA, a ligand for Toll-like Receptor 3 (TLR3) and the cytoplasmic RNA receptors RIG1 and MDA5, activate a signaling network in which the IKK-related protein kinase TBK1 phosphorylates the transcription factor Interferon Regulatory Factor 3 (IRF3) and the E3 ubiquitin ligase Pellino1. IRF3 then translocates to the nucleus where it stimulates transcription of the interferon beta (IFN beta) gene, but the function of Pellino1 in this pathway is unknown. Here, we report that myeloid cells and embryonic fibroblasts from knock-in mice expressing an E3 ligase-deficient mutant of Pellino1 produce reduced levels of IFN beta mRNA and secrete much less IFN beta in response to viral double-stranded RNA because the interaction of IRF3 with the IFN beta promoter is impaired. These results identify Pellino1 as a novel component of the signal transduction network by which viral double-stranded RNA stimulates IFN beta gene transcription.

    Original languageEnglish
    Pages (from-to)34825-34835
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume287
    Issue number41
    DOIs
    Publication statusPublished - 2012

    Cite this

    Enesa, K., Ordureau, A., Smith, H., Barford, D., Cheung, P. C. F., Patterson-Kane, J., Arthur, J. S. C., & Cohen, P. (2012). Pellino1 Is Required for Interferon Production by Viral Double-stranded RNA. Journal of Biological Chemistry, 287(41), 34825-34835. https://doi.org/10.1074/jbc.M112.367557