Source:http://linkedlifedata.com/resource/pubmed/id/17906119
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-12-24
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pubmed:abstractText |
A375-6 human melanoma cells are sensitive to the antiproliferative effect of IL-1. After a long period of culturing, we have obtained cells resistant to IL-1. The resistant clone A375-R8 constitutively produced IL-1 alpha. In this study, we identified a sequence, CGCC, located at -48 to -45 upstream of the transcription start site, to be essential for the constitutive IL-1 alpha gene activation. Specificity protein 1 (Sp1) and Sp3 bound to the nucleotide containing the sequence. Although the binding level to the nucleotide and expression level of Sp1 and Sp3 are comparable in A375-R8 and A375-6 cells, transactivation activity of Sp1 is higher in A375-R8 cells as compared with A375-6 cells. Sp3 could not transactivate the IL-1 alpha promoter. These results suggest that Sp1 but not Sp3 is important for IL-1 alpha gene activation. Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), greatly augmented the IL-1 alpha promoter activity in A375-6 cells to the level comparable with that in A375-R8 cells. TSA also induced IL-1 alpha mRNA expression in A375-6 cells. Sp1 and Sp3 bound to HDAC1 in A375-R8 and A375-6 cells. The chromatin immunoprecipitation assay revealed the binding of Sp1 and HDAC1 to the promoter region of the IL-1 alpha gene. The activities of HDAC bound to Sp1 and Sp3, and that of HDAC1 was lower in A375-R8 cells as compared with A375-6 cells. These results indicate that the reduction in the activity and interaction of HDAC1 with Sp1 are critical for the constitutive IL-1 alpha gene expression.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 Transcription Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0741-5400
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
190-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17906119-Cell Line, Tumor,
pubmed-meshheading:17906119-DNA,
pubmed-meshheading:17906119-Enzyme Activation,
pubmed-meshheading:17906119-Gene Expression Profiling,
pubmed-meshheading:17906119-Histone Deacetylase 1,
pubmed-meshheading:17906119-Histone Deacetylases,
pubmed-meshheading:17906119-Humans,
pubmed-meshheading:17906119-Interleukin-1alpha,
pubmed-meshheading:17906119-Melanoma,
pubmed-meshheading:17906119-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17906119-Sp1 Transcription Factor,
pubmed-meshheading:17906119-Sp3 Transcription Factor,
pubmed-meshheading:17906119-Tumor Cells, Cultured
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pubmed:year |
2008
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pubmed:articleTitle |
The interaction with Sp1 and reduction in the activity of histone deacetylase 1 are critical for the constitutive gene expression of IL-1 alpha in human melanoma cells.
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pubmed:affiliation |
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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