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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1996-12-30
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pubmed:abstractText |
Expression of the gene encoding PTH-related peptide (PTHrP), a protein that plays a primary role in the development of humoral hypercalcemia of malignancy, is down-regulated at the transcriptional level by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Deletions of the 5'-flanking region of the rat PTHrP gene, when fused to the chloramphenicol acetyl-transferase gene and transfected into ROS 17/2.8 (rat osteosarcoma) cells, showed that the 1,25-(OH)2D3 responsive region is located between -1.05 and -0.71 kb upstream of the transcription start site. Further mapping of this region revealed that a 123-bp fragment is able to confer 1,25-(OH)2D3 responsiveness to a heterologous (SV40) promoter. This region contains two potential vitamin D response elements (VDREs). One of these motifs resembles the negative VDRE (nVDRE) from the PTH gene, which is also down-regulated by vitamin D3. The other element resembles the canonical VDRE (two hexanucleotide motifs separated by three nucleotides), which has been characterized in a number of genes whose expression is modulated by vitamin D3. Electrophoretic mobility shift assays using nuclear extracts from ROS 17/2,8 cells and from vitamin D receptor. (VDR)-enriched COS 1 cells revealed that both elements interact with the VDR. This protein-DNA interaction is disrupted by an anti-VDR antibody. Therefore, modulation of PTHrP gene transcription by 1,25-(OH)2D3 is mediated by the VDR interacting with one or both of the identified motifs in the 5'-flanking sequence of the gene.
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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/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone-Related Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin D
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0888-8809
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
672-81
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8776727-Animals,
pubmed-meshheading:8776727-Base Sequence,
pubmed-meshheading:8776727-Binding Sites,
pubmed-meshheading:8776727-Calcitriol,
pubmed-meshheading:8776727-Down-Regulation,
pubmed-meshheading:8776727-Electrophoresis,
pubmed-meshheading:8776727-Gene Expression Regulation,
pubmed-meshheading:8776727-Parathyroid Hormone-Related Protein,
pubmed-meshheading:8776727-Proteins,
pubmed-meshheading:8776727-Rats,
pubmed-meshheading:8776727-Receptors, Calcitriol,
pubmed-meshheading:8776727-Sequence Homology, Nucleic Acid,
pubmed-meshheading:8776727-Transcription, Genetic,
pubmed-meshheading:8776727-Vitamin D
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pubmed:year |
1996
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pubmed:articleTitle |
DNA sequences in the rat parathyroid hormone-related peptide gene responsible for 1,25-dihydroxyvitamin D3-mediated transcriptional repression.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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