DEAF1 is a Pellino1-interacting protein required for interferon production by Sendai virus and double-stranded RNA

Alban Ordureau, Karine Enesa, Sambit Nanda, Brice Le Francois, Mark Peggie, Alan Prescott, Paul R. Albert, Philip Cohen

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    Abstract

    Double-stranded (ds) RNA of viral origin, a ligand for Melanoma Differentiation-associated gene 5 (MDA5) and Toll-Like Receptor 3 (TLR3), induces the TANK-Binding Kinase 1 (TBK1)-dependent phosphorylation and activation of Interferon Regulatory Factor 3 (IRF3) and the E3 ubiquitin ligase Pellino1, which are required for interferon ß (IFNß) gene transcription. Here, we report that Pellino1 interacts with the transcription factor Deformed Epidermal Autoregulatory Factor 1 (DEAF1). The interaction is independent of the E3 ligase activity of Pellino1, but weakened by the phosphorylation of Pellino1. We show that DEAF1 binds to the IFNß promoter and to IRF3 and IRF7, that it is required for the transcription of the IFNß gene and IFNß secretion in MEFs infected with Sendai virus or transfected with poly(I:C). DEAF1 is also needed for TLR3-dependent IFNß production. Taken together, our results identify DEAF1 as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFNß production.
    Original languageEnglish
    Pages (from-to)24569-24580
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume288
    Issue number34
    DOIs
    Publication statusPublished - 23 Aug 2013

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    Keywords

    • Animals
    • DEAD-box RNA Helicases
    • HEK293 Cells
    • Humans
    • Interferon Regulatory Factor-3
    • Interferon-beta
    • Mice
    • Nuclear Proteins
    • Protein-Serine-Threonine Kinases
    • RNA, Double-Stranded
    • Respirovirus Infections
    • Sendai virus
    • Signal Transduction
    • Toll-Like Receptor 3
    • Transcription Factors
    • Transcription, Genetic
    • Ubiquitin-Protein Ligases

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