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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2000-9-5
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pubmed:abstractText |
The divergent homeobox gene Hex is expressed in both developing and mature liver. A putative Hex binding site was identified in the promoter region of the liver-specific Na(+)-bile acid cotransporter gene (ntcp), and we hypothesized that Hex regulates the ntcp promoter through this site. Successive 5'-deletions of the ntcp promoter in a luciferase reporter construct transfected into Hep G2 cells confirmed a Hex response element (HRE) within the ntcp promoter (nt -733/-714). Moreover, p-CMHex transactivated a heterologous promoter construct containing HRE multimers (p4xHRELUC), whereas a 5-bp mutation of the core HRE eliminated transactivation. A dominant negative form of Hex (p-Hex-DN) suppressed basal luciferase activity of p-4xHRELUC and inhibited activation of this construct by p-CMHex. Interestingly, p-CMHex transactivated the HRE in Hep G2 cells but not in fibroblast-derived COS cells, suggesting the possibility that Hex protein requires an additional liver cell-specific factor(s) for full activity. Electrophoretic mobility shift assays confirmed that liver and Hep G2 cells contain a specific nuclear protein that binds the native HRE. We have demonstrated that the liver-specific ntcp gene promoter is the first known target of Hex and is a useful tool for evaluating function of the Hex protein.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HHEX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hhex protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotide Probes,
http://linkedlifedata.com/resource/pubmed/chemical/Organic Anion Transporters...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/sodium-bile acid cotransporter
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G347-55
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pubmed:dateRevised |
2010-8-9
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pubmed:meshHeading |
pubmed-meshheading:10915644-Animals,
pubmed-meshheading:10915644-Base Sequence,
pubmed-meshheading:10915644-COS Cells,
pubmed-meshheading:10915644-Carrier Proteins,
pubmed-meshheading:10915644-Gene Expression Regulation,
pubmed-meshheading:10915644-Genetic Complementation Test,
pubmed-meshheading:10915644-Hepatoblastoma,
pubmed-meshheading:10915644-Homeodomain Proteins,
pubmed-meshheading:10915644-Humans,
pubmed-meshheading:10915644-Liver,
pubmed-meshheading:10915644-Liver Neoplasms,
pubmed-meshheading:10915644-Membrane Transport Proteins,
pubmed-meshheading:10915644-Molecular Sequence Data,
pubmed-meshheading:10915644-Mutagenesis,
pubmed-meshheading:10915644-Oligonucleotide Probes,
pubmed-meshheading:10915644-Organic Anion Transporters, Sodium-Dependent,
pubmed-meshheading:10915644-Promoter Regions, Genetic,
pubmed-meshheading:10915644-Rats,
pubmed-meshheading:10915644-Recombinant Fusion Proteins,
pubmed-meshheading:10915644-Symporters,
pubmed-meshheading:10915644-Transcription, Genetic,
pubmed-meshheading:10915644-Transcription Factors,
pubmed-meshheading:10915644-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Divergent homeobox gene hex regulates promoter of the Na(+)-dependent bile acid cotransporter.
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pubmed:affiliation |
Department of Pediatrics, Yale University, New Haven, CT 06520-8064, USA.
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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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