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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/33691

Title: 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-kappa
Author: O'NEILL, LUKE ANTHONY JOHN
Sponsor: Science Foundation Ireland
Author's Homepage: http://people.tcd.ie/laoneill
Keywords: Biochemistry
Issue Date: 2003
Publisher: The American Society for Biochemistry and Molecular Biology
Citation: C. Wietek, S. M. Miggin, C. A. Jefferies and L. A. O'Neill ‘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-kappa’ in The Journal of Biological Chemistry, 278, (51), 2003, pp 50923-50931
Series/Report no.: The Journal of Biological Chemistry
278
51
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 IκB kinase 2 and a mutant form of IκB, which acts as a super-repressor of NF-κB, 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 NF-κB 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-3-mediated activation of the ISRE by TLR4 but not TLR3 requires the p65 subunit of NF-κB.
Description: PUBLISHED
URI: http://dx.doi.org/10.1074/jbc.M308135200
http://hdl.handle.net/2262/33691
Appears in Collections:Biochemistry (Scholarly Publications)

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