title: DEAF1 is a Pellino1-interacting protein required for interferon production by Sendai virus and double-stranded RNA.
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.
authors.affiliation: MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
authors.forename: Alban
authors.initials: A
authors.lastname: Ordureau
authors.forename: Karine
authors.initials: K
authors.lastname: Enesa
authors.forename: Sambit
authors.initials: S
authors.lastname: Nanda
authors.forename: Brice
authors.initials: B
authors.lastname: Le Francois
authors.forename: Mark
authors.initials: M
authors.lastname: Peggie
authors.forename: Alan
authors.initials: A
authors.lastname: Prescott
authors.forename: Paul R
authors.initials: PR
authors.lastname: Albert
authors.forename: Philip
authors.initials: P
authors.lastname: Cohen
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D010253:Respirovirus Infections / Q000235:genetics / Q000378:metabolism*; D029082:Sendai virus / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C116013:DEAF1 protein, human; D004268:DNA-Binding Proteins; C548809:Deaf1 protein, mouse; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014157:Transcription Factors; D016899:Interferon-beta; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C452815:IFIH1 protein, human; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; C418046:Peli1 protein, mouse
keywords: Cytokines/Interferon; DEAF1; Double-stranded RNA Viruses; Fibroblast; IRF3; Interferon; Pellino1; TBK1; Transcription Factors