DEAF1 Is a Pellino1-interacting Protein Required for Interferon Production by Sendai Virus and Double-stranded RNA |
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| Authors: | Alban Ordureau Karine Enesa Sambit Nanda Brice Le Francois Mark Peggie Alan Prescott Paul R. Albert Philip Cohen |
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| Affiliation: | From the ‡MRC Protein Phosphorylation and Ubiquitylation Unit and ;¶College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom and ;the §Ottawa Hospital Research Institute (Neuroscience), Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada |
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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 β (IFNβ) 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 IFNβ promoter and to IRF3 and IRF7, that it is required for the transcription of the IFNβ gene and IFNβ secretion in MEFs infected with Sendai virus or transfected with poly(I:C). DEAF1 is also needed for TLR3-dependent IFNβ production. Taken together, our results identify DEAF1 as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFNβ production. |
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| Keywords: | Cytokines/Interferon Double-stranded RNA Viruses Fibroblast Interferon Transcription Factors DEAF1 IRF3 Pellino1 TBK1 |
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