Peer-Reviewed Journal Details
Mandatory Fields
Siednienko J.;Maratha A.;Yang S.;Mitkiewicz M.;Miggin S.;Moynagh P.
2011
December
Journal of Biological Chemistry
Nuclear factor κB subunits RelB and cRel negatively regulate toll-like receptor 3-mediated β-interferon production via induction of transcriptional repressor protein YY1
Published
()
Optional Fields
286
52
44750
44763
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-βB, and ATF-2/c-Jun on the IFN-β promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-βB 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-βexpression 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-βpromoter 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-βexpression. 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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
0021-9258
10.1074/jbc.M111.250894
Grant Details