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    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


    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:

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