Peer-Reviewed Journal Details
Mandatory Fields
Siednienko, J;Maratha, A;Yang, S;Mitkiewicz, M;Miggin, SM;Moynagh, PN
2011
December
Journal of Biological Chemistry
Nuclear Factor kappa B Subunits RelB and cRel Negatively Regulate Toll-like Receptor 3-mediated beta-Interferon Production via Induction of Transcriptional Repressor Protein YY1
Published
19 ()
Optional Fields
MYD88 ADAPTER-LIKE I INTERFERONS SIGNALING PATHWAY IMMUNE-RESPONSES GENE INDUCTION PROMOTER EXPRESSION IDENTIFICATION AUTOIMMUNITY ENHANCEOSOME
286
44750
44763
The induction of beta-interferon (IFN-beta) is a key anti-viral response to infection by RNA viruses. Virus-induced expression of IFN-beta requires the co-operative action of the transcription factors IRF-3/7, NF-kappa B, and ATF-2/c-Jun on the IFN-beta promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-kappa B and promote its binding to the IFN-beta promoter, recent studies have indicated that NF-kappa B is not essential for virus-induced expression of IFN-beta. Herein, we examined the role of NF-kappa B in regulating IFN-beta expression in response to the viral-sensing Toll-like receptor 3 (TLR3). Intriguingly pharmacological inhibition of the NF-kappa B pathway augments late phase expression of IFN-beta expression in response to TLR3 stimulation. We show that the negative effect of NF-kappa B on IFN-beta 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-beta promoter and inhibits the binding of IRF7 to the latter. Evidence is also presented showing that the NF-kappa B subunits c-Rel and RelB are the likely key drivers of these negative effects on IFN-beta 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-beta expression.
BETHESDA
0021-9258
10.1074/jbc.M111.250894
Grant Details