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    Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ϵ-dependent Induction of Sp1 Protein and Interleukin 15


    Doyle, Sarah L. and Shirey, Kari Ann and McGettrick, Anne F. and Kenny, Elaine F. and Carpenter, Susan B. and Caffrey, Brian E. and Gargan, Siobhan and Quinn, Susan R. and Caamano, Jorge H. and Moynagh, Paul N. and Vogel, Stefanie N. and O'Neill, Luke A. (2013) Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ϵ-dependent Induction of Sp1 Protein and Interleukin 15. Journal of Biological Chemistry, 288. 25066 -25075. ISSN 0021-9258

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    Abstract

    In this study we describe a previously unreported function for NFκB2, an NFκB family transcription factor, in antiviral immunity. NFκB2 is induced in response to poly(I:C), a mimic of viral dsRNA. Poly(I:C), acting via TLR3, induces p52-dependent transactivation of a reporter gene in a manner that requires the kinase activity of IκB kinase ϵ (IKKϵ) and the transactivating potential of RelA/p65. We identify a novel NFκB2 binding site in the promoter of the transcription factor Sp1 that is required for Sp1 gene transcription activated by poly(I:C). We show that Sp1 is required for IL-15 induction by both poly(I:C) and respiratory syncytial virus, a response that also requires NFκB2 and IKKϵ. Our study identifies NFκB2 as a target for IKKϵ in antiviral immunity and describes, for the first time, a role for NFκB2 in the regulation of gene expression in response to viral infection.

    Item Type: Article
    Keywords: Cytokine Induction; Gene Regulation; Innate Immunity; Molecular Biology; NF-κB; Signal Transduction; Sp1; Toll-like Receptor (TLR); Transcription; Viral Immunology;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11035
    Identification Number: https://doi.org/10.1074/jbc.M113.469122
    Depositing User: Professor Paul Moynagh
    Date Deposited: 11 Sep 2019 13:20
    Journal or Publication Title: Journal of Biological Chemistry
    Publisher: American Society for Biochemistry and Molecular Biology
    Refereed: Yes
    Funders: National Institutes of Health, Science Foundation Ireland (SFI), European Union FP7 INFLA-CARE Collaborative Research Program, Biotechnology and Biological Sciences Research Council, School of Immunity and Infection, College of Medicine, University of Birmingham
    URI:

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