Wietek, Claudia and Miggin, Sinead and Jefferies, Caroline and O'Neill, Luke A.J. (2003) Interferon Regulatory Factor-3-mediated Activation of the Interferon-sensitive Response Element by Toll-like receptor (TLR) 4 but Not TLR3 Requires the p65 Subunit of NF-κB. Journal of Biological Chemistry, 278 (51). pp. 50923-50931. ISSN 0021-9258

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Abstract

Interferon regulatory factor (IRF) 3 is a transcription factor that binds the interferon-sensitive response element (ISRE) and is activated by Toll-like receptor 3 (TLR3) and TLR4. We have found that a dominant negative form of I κB kinase 2 and a mutant form of Iκ B, which acts as a super-repressor of NFκ B, blocked activation of the ISRE by the TLR4 ligand lipopolysaccharide but not the TLR3 ligand poly(I-C). TLR4 failed to activate the ISRE in mouse embryonic fibroblasts bearing a targeted deletion of p65, whereas the response to TLR3 in these cells was normal. The p65 subunit of NFκ B was detected in the lipopolysaccharide-activated but not poly(I-C)-activated ISRE-binding complex. Finally, p65 promoted transactivation of gene expression by IRF-3. These results therefore indicate that IRF-3mediated activation of the ISRE by TLR4 but not TLR3 requires the p65 subunit of NFκB.

Item Type:	Article
Keywords:	Interferon Regulatory; Factor-3-mediated Activation; Interferon-sensitive; Response Element; Toll-like; receptor TLR4; TLR3; p65 Subunit; NF-κB
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12631
Identification Number:	https://doi.org/10.1074/jbc.M308135200
Depositing User:	Sinead Miggin
Date Deposited:	26 Mar 2020 16:02
Journal or Publication Title:	Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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