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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

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 r...

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Bibliographic Details
Published in:The Journal of biological chemistry 2013-08, Vol.288 (35), p.25066-25075
Main Authors: Doyle, Sarah L., Shirey, Kari Ann, McGettrick, Anne F., Kenny, Elaine F., Carpenter, Susan, Caffrey, Brian E., Gargan, Siobhan, Quinn, Susan R., Caamaño, Jorge H., Moynagh, Paul, Vogel, Stefanie N., O'Neill, Luke A.
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Language:English
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Summary: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. Background: IKKϵ can promote the ability of p52 to transactivate gene expression in a manner requiring p65. Results: p52 is induced by TLR3 activation and regulates Sp1 transcription. Sp1 promotes the transcription of IL-15. Both events require the presence of IKKϵ and p52. Conclusion: p52 is a target for IKKϵ in antiviral immunity. Significance: This study reports a role for NFκB2 in the induction of antiviral gene expression.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M113.469122