Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase epsilon-dependent induction of Sp1 protein and interleukin 15

Sarah L Doyle, Kari Ann Shirey, Anne F McGettrick, Elaine F Kenny, Susan Carpenter, Brian E Caffrey, Siobhan Gargan, Susan R Quinn, Jorge H Caamaño, Paul Moynagh, Stefanie N Vogel, Luke A O'Neill

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)25066-75
Number of pages10
JournalThe Journal of biological chemistry
Volume288
Issue number35
DOIs
Publication statusPublished - 30 Aug 2013

Keywords

  • Animals
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase
  • Interferon Inducers
  • Interleukin-15
  • Mice
  • Mice, Knockout
  • NF-kappa B p52 Subunit
  • Poly I-C
  • Respiratory Syncytial Virus Infections
  • Respiratory Syncytial Viruses
  • Response Elements
  • Sp1 Transcription Factor
  • Toll-Like Receptor 3
  • Transcription Factor RelA
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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