Nuclear factor κB subunits RelB and cRel negatively regulate Toll-like receptor 3-mediated ß-interferon production via induction of transcriptional repressor protein YY1.
J Biol Chem
; 286(52): 44750-63, 2011 Dec 30.
Article
in En
| MEDLINE
| ID: mdl-22065573
The induction of ß-interferon (IFN-ß) is a key anti-viral response to infection by RNA viruses. Virus-induced expression of IFN-ß requires the co-operative action of the transcription factors IRF-3/7, NF-κB, and ATF-2/c-Jun on the IFN-ß promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-κB and promote its binding to the IFN-ß promoter, recent studies have indicated that NF-κB is not essential for virus-induced expression of IFN-ß. Herein, we examined the role of NF-κB in regulating IFN-ß 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-ß expression in response to TLR3 stimulation. We show that the negative effect of NF-κB on IFN-ß 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-ß 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-ß 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-ß expression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Nuclear Proteins
/
Interferon-beta
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DNA-Binding Proteins
/
YY1 Transcription Factor
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Transcription Factor RelB
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Toll-Like Receptor 3
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Document type:
Article
Affiliation country:
Ireland
Country of publication:
United States