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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1995-4-5
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pubmed:abstractText |
Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine biosynthesis. We investigated the transcriptional regulation of the rat ODC gene using transient expression assays. The 5'-flanking region (-1156 to +13) of the ODC gene was sufficient to mediate strong basal expression of a luciferase reporter. Sequences between -345 and -93 contributed to basal promoter activity. This region, containing five potential Sp1 binding sites, was analyzed by electrophoretic mobility shift assays. Three specific DNA-protein complexes were identified using H35 nuclear extracts and the -345/-93 ODC probe. Binding to all three was eliminated by competition with an oligonucleotide containing an Sp1 binding site, but not by a mutant Sp1 oligonucleotide. Preincubation with an antibody against Sp1 supershifted complexes associated with one or more of Sp1 binding sites 1-4 as well as with site 5. DNase I footprinting revealed two protected regions: PR-I (-92 to -130) and PR-II (-304 to -332). PR-I contains a putative binding site for Sp1 that was protected by recombinant Sp1 protein. Transfection studies in Schneider SL2 cells demonstrated that the ODC promoter is transactivated up to 350-fold by Sp1 and that this transactivation is dependent on the presence of Sp1 binding sites 1-4. Thus, although the ODC promoter binds multiple nuclear proteins, Sp1 or a related protein appears to be a critical determinant of ODC transcription, possibly through cooperative interactions between Sp1 and additional transcription factors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
3
|
pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4341-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7876196-Animals,
pubmed-meshheading:7876196-Antigens,
pubmed-meshheading:7876196-Binding, Competitive,
pubmed-meshheading:7876196-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:7876196-Nuclear Proteins,
pubmed-meshheading:7876196-Ornithine Decarboxylase,
pubmed-meshheading:7876196-Promoter Regions, Genetic,
pubmed-meshheading:7876196-Protein Binding,
pubmed-meshheading:7876196-Rats,
pubmed-meshheading:7876196-Sp1 Transcription Factor,
pubmed-meshheading:7876196-Transcriptional Activation,
pubmed-meshheading:7876196-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Regulation of rat ornithine decarboxylase promoter activity by binding of transcription factor Sp1.
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pubmed:affiliation |
University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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