Source:http://linkedlifedata.com/resource/pubmed/id/16225938
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2005-11-29
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| pubmed:abstractText |
The human reduced folate carrier (hRFC) gene has a complex regulation involving 6 alternatively spliced non-coding exons and promoters (A1/A2, A, B, C, D, and E). The hRFC-A1/A2 promoter is unique in that it transcribes a novel transcript with an in-frame AUG in non-coding exon A1/A2 that encodes a modified hRFC protein with altered transport function. In this report, we characterize the hRFC-A1/A2 promoter in HepG2 human hepatoma cells. By transfecting HepG2 cells with 5' and 3' deletion constructs, a transcriptionally important 270 bp region was identified. Gel shift assays identified transcription factor binding to three E-box elements and one GATA site within this region. These elements were verified by transfections of mutant constructs into HepG2 cells. Cotransfections in Drosophila Mel-2 cells confirmed promoter activation by USF1 and GATA1. A physical association between USF1 and GATA1 was demonstrated by their co-immunoprecipitation. By real time PCR analysis of transfected HepG2 cells, USF1 and GATA1 increased endogenous hRFC-A1/A2 transcripts. Altogether, our results demonstrate a transcriptionally important region in the hRFC-A1/A2 promoter including E-box and GATA elements, and a transactivation by USF1 and GATA1 proteins. Our results further establish the complexity of hRFC regulation, as a means of ensuring adequate folate cofactor transport for cell proliferation.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GATA Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLC19A2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Upstream Stimulatory Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0006-3002
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
1731
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
115-24
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16225938-Animals,
pubmed-meshheading:16225938-Cell Proliferation,
pubmed-meshheading:16225938-Cells, Cultured,
pubmed-meshheading:16225938-DNA-Binding Proteins,
pubmed-meshheading:16225938-Drosophila,
pubmed-meshheading:16225938-E-Box Elements,
pubmed-meshheading:16225938-Exons,
pubmed-meshheading:16225938-GATA Transcription Factors,
pubmed-meshheading:16225938-Gene Expression Regulation,
pubmed-meshheading:16225938-Genes, Reporter,
pubmed-meshheading:16225938-Humans,
pubmed-meshheading:16225938-Membrane Transport Proteins,
pubmed-meshheading:16225938-Promoter Regions, Genetic,
pubmed-meshheading:16225938-Transcription, Genetic,
pubmed-meshheading:16225938-Transcriptional Activation,
pubmed-meshheading:16225938-Transfection,
pubmed-meshheading:16225938-Tumor Cells, Cultured,
pubmed-meshheading:16225938-Upstream Stimulatory Factors
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| pubmed:year |
2005
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| pubmed:articleTitle |
Transcriptional regulation of the human reduced folate carrier A1/A2 promoter: Identification of critical roles for the USF and GATA families of transcription factors.
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| pubmed:affiliation |
Department of Pharmacology, Barbara Ann Karmanos Cancer Institute, and Wayne State University School of Medicine, Detroit, MI 48201, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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