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Nuclear Factor κB Subunits RelB and cRel Negatively Regulate Toll-like Receptor 3-mediated β-Interferon Production via Induction of Transcriptional Repressor Protein YY1
Siednienko, Jakub; Maratha, Ashwini; Yang, Shuo; Mitkiewicz, Malgorzata; Miggin, Sinead; Moynagh, Paul N.
The induction of β-interferon (IFN-β) is a key anti-viral response to infection by RNA viruses. Virus-induced expression of IFN-β requires the co-operative action of the transcription factors IRF-3/7, NF-κB, and ATF-2/c-Jun on the IFN-β promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-κB and promote its binding to the IFN-β promoter, recent studies have indicated that NF-κB is not essential for virus-induced expression of IFN-β. Herein, we examined the role of NF-κB in regulating IFN-β expression in response to the viral-sensing Toll-like receptor 3 (TLR3). Intriguingly pharmacological inhibition of the NF-κB pathway augments late phase expression of IFN-β expression in response to TLR3 stimulation. We show that the negative effect of NF-κB on IFN-β expression is dependent on the induction of the transcriptional repressor protein YinYang1. We demonstrate that the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) induces expression and nuclear translocation of YinYang1 where it interacts with the IFN-β promoter and inhibits the binding of IRF7 to the latter. Evidence is also presented showing that the NF-κB subunits c-Rel and RelB are the likely key drivers of these negative effects on IFN-β expression. These findings thus highlight for the first time a novel self-regulatory mechanism that is employed by TLR3 to limit the level and duration of IFN-β expression.
Keyword(s): Nuclear Factor κB; RelB; cRel; Negatively Regulate Toll-like Receptor; 3-mediated; β-Interferon; Production via Induction; Transcriptional Repressor Protein YY1
Publication Date:
2011
Type: Journal article
Peer-Reviewed: Yes
Institution: Maynooth University
Citation(s): Siednienko, Jakub and Maratha, Ashwini and Yang, Shuo and Mitkiewicz, Malgorzata and Miggin, Sinead and Moynagh, Paul N. (2011) Nuclear Factor κB Subunits RelB and cRel Negatively Regulate Toll-like Receptor 3-mediated β-Interferon Production via Induction of Transcriptional Repressor Protein YY1. Journal of Biological Chemistry, 286 (52). pp. 44750-44763. ISSN 0021-9258
Publisher(s): American Society for Biochemistry and Molecular Biology
File Format(s): other
Related Link(s): https://mural.maynoothuniversity.ie/9129/1/PM_nuclear%202011.pdf
First Indexed: 2020-04-02 06:24:24 Last Updated: 2021-07-31 07:49:47