DEAF1 is a pellino 1-interacting protein required for interferon production by Sendai virus and double-stranded RNA

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Abstract

Background: The E3 ligase Pellino1 is required for interferon (IFN) β production following infection with Sendai virus or poly(I:C). Results: The transcription factor DEAF1 interacts with Pellino1 and, like Pellino1, is needed for transcription of the IFNβ gene. Conclusion: DEAF1 is required for the production of IFNβ . Significance: DEAF1 is a new signaling component required for IFNβ production. 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 DEAF1as a novel component of the signal transduction network by which dsRNA of viral origin stimulates IFNβ production. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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Ordureau, A., Enesa, K., Nanda, S., Le Francois, B., Peggie, M., Prescott, A., … Cohen, P. (2013). DEAF1 is a pellino 1-interacting protein required for interferon production by Sendai virus and double-stranded RNA. Journal of Biological Chemistry, 288(34), 24569–24580. https://doi.org/10.1074/jbc.M113.479550

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