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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1997-11-20
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pubmed:abstractText |
Dihydrofolate reductase activity is required for many biosynthetic pathways including nucleotide synthesis. Its expression is therefore central to cellular growth, and it has become a key target for cancer chemotherapy. Transcription of the dihydrofolate reductase gene is regulated with growth, being expressed maximally in late G1/early S phase following serum stimulation of quiescent cells. This regulation is directed by a promoter which contains binding sites for only the transcription factors Sp1 and E2F. In this study, the role of these promoter elements in growth/cell cycle regulation of dihydrofolate transcription was addressed directly by transient transfection of Balb/c 3T3 cells with mutant promoter-reporter gene constructs. The E2F sites were found to repress transcription in G0 and early G1 but did not contribute to the level of transcription in late G1/S phase. In contrast, Sp1 sites were able to mediate induction of transcription from the dihydrofolate reductase promoter, as well as a heterologous promoter, following serum stimulation of quiescent cells. These findings add dihydrofolate reductase to a growing list of genes at which E2F sites are primarily repressive elements and delineate a role for Sp1 sites in the growth/cell cycle regulation of transcription.
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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/Arid4a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma-Binding Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydrofolate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor DP1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0730-2312
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
24-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9328836-3T3 Cells,
pubmed-meshheading:9328836-Animals,
pubmed-meshheading:9328836-Binding Sites,
pubmed-meshheading:9328836-Blood,
pubmed-meshheading:9328836-Carrier Proteins,
pubmed-meshheading:9328836-Cell Cycle,
pubmed-meshheading:9328836-Cell Cycle Proteins,
pubmed-meshheading:9328836-Cell Division,
pubmed-meshheading:9328836-Cricetinae,
pubmed-meshheading:9328836-DNA-Binding Proteins,
pubmed-meshheading:9328836-E2F Transcription Factors,
pubmed-meshheading:9328836-Mice,
pubmed-meshheading:9328836-Promoter Regions, Genetic,
pubmed-meshheading:9328836-Recombinant Fusion Proteins,
pubmed-meshheading:9328836-Retinoblastoma-Binding Protein 1,
pubmed-meshheading:9328836-Sp1 Transcription Factor,
pubmed-meshheading:9328836-Tetrahydrofolate Dehydrogenase,
pubmed-meshheading:9328836-Transcription, Genetic,
pubmed-meshheading:9328836-Transcription Factor DP1,
pubmed-meshheading:9328836-Transcription Factors
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pubmed:year |
1997
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pubmed:articleTitle |
Distinct roles for Sp1 and E2F sites in the growth/cell cycle regulation of the DHFR promoter.
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pubmed:affiliation |
Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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