Source:http://linkedlifedata.com/resource/pubmed/id/11034398
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2000-10-16
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| pubmed:abstractText |
The present study investigates the regulatory mechanisms involved in the cooperation between IFN-gamma and TNF-alpha to promote transcription from IFN regulatory factor-1 (IRF-1). A transient transfection analysis revealed that the region between -218 and -144, where +1 is the transcription start site, as well as previously reported downstream elements, ppkappaB and IFN-gamma activation site/kappaB, were required for the optimal response to the two cytokines. A subsequent DNase I footprint analysis showed that the region between -171 and -144 was inducibly protected with stimulation by TNF-alpha, and this protection was significantly enhanced with the combination of IFN-gamma and TNF-alpha. In an EMSA with the protected region as a probe, a TNF-alpha-inducible complex (C1) and an IFN-gamma-inducible complex (C2), but no synergy-specific DNA-protein complexes, were recognized. The C1 complex consisted of a pre-existing factor (p65/p50), whereas the C2 complex consisted of a newly synthesized IRF-1-related factor. A methylation interference assay revealed the critical G residues (from -167 to -151) for the DNA-protein complex formation specific to the cytokine response, and within this region the novel kappaB sequence, the promoter distal kappaB (pdkappaB) element (5'-GGGGAAG TAC-3'), was identified. Because the base substitutions over the pdkappaB region (from -171 to -144) affected not only the TNF-alpha-response but also that of IFN-gamma, this region might contribute to the cooperative action of the NF-kappaB subunits with the IRF-1-related factor. Finally, we demonstrated that none of the cis-acting elements, ppkappaB, pdkappaB, or IFN-gamma activation site/kappaB, is dispensable for the optimal synergism in response to IFN-gamma and TNF-alpha.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
165
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3907-16
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11034398-Adjuvants, Immunologic,
pubmed-meshheading:11034398-Binding Sites,
pubmed-meshheading:11034398-Cells, Cultured,
pubmed-meshheading:11034398-Cytokines,
pubmed-meshheading:11034398-DNA-Binding Proteins,
pubmed-meshheading:11034398-Gene Expression Regulation,
pubmed-meshheading:11034398-Humans,
pubmed-meshheading:11034398-Interferon Regulatory Factor-1,
pubmed-meshheading:11034398-Interferon-gamma,
pubmed-meshheading:11034398-K562 Cells,
pubmed-meshheading:11034398-NF-kappa B,
pubmed-meshheading:11034398-NF-kappa B p50 Subunit,
pubmed-meshheading:11034398-Phosphoproteins,
pubmed-meshheading:11034398-Promoter Regions, Genetic,
pubmed-meshheading:11034398-Response Elements,
pubmed-meshheading:11034398-Transcription, Genetic,
pubmed-meshheading:11034398-Transcription Factor RelA,
pubmed-meshheading:11034398-Transcription Factors,
pubmed-meshheading:11034398-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11034398-U937 Cells
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| pubmed:year |
2000
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| pubmed:articleTitle |
Identification of a novel cytokine response element in the human IFN regulatory factor-1 gene promoter.
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| pubmed:affiliation |
Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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