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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2004-4-6
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pubmed:abstractText |
The sterol regulatory element-binding protein-1c (SREBP-1c), as well as SREBP-1a and SREBP-2, inhibit transcription of the gene encoding the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C). There are two SREBP regulatory elements (SREs) in the PEPCK-C gene promoter (-322 to -313 and -590 to -581). The SRE at -590 overlaps an Sp1 site on the opposite strand of the DNA. These SREs bound SREBP-1a and SREBP-1c with low affinity but the addition of purified upstream stimulatory activity enhanced the binding of SREBP-1 to both of these sites. Mutating these SREs increased both unstimulated (5-fold) and protein kinase A-stimulated transcription (8-27-fold) from the PEPCK-C gene promoter; this was lost when both SREs were mutated. The SRE at -590 differs by a single base pair from the SRE in the low density lipoprotein (LDL) receptor gene (T in the PEPCK-C gene promoter at -582, compared with an A in the SRE of the gene for the LDL receptor promoter). Introduction of the LDL receptor SRE into the PEPCK-C gene promoter increased SREBP-1c binding and caused a 10-fold enhancement of basal transcription from the promoter, rather than an inhibition as observed with the SRE in the PEPCK-C gene promoter. The T/A change does not alter the binding of Sp1 to its site on the opposite strand of the DNA. Sp1 bound to the promoter independently of SREBP-1c but competed with SREBP-1c for binding. Sp1 does not bind to the SRE at -322. Chromatin immunoprecipitation analysis, using rat hepatocytes, demonstrated that SREBP-1 and Sp1 were associated in vivo with putative regulatory regions corresponding to the SREs in the PEPCK-C gene promoter. We propose that insulin represses transcription of the gene for PEPCK-C by inducing SREBP-1c production in the liver, which interferes with the stimulatory effect of Sp1 at -590 of the PEPCK-C gene promoter.
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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/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoenolpyruvate Carboxykinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoenolpyruvate carboxykinase...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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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 |
15385-95
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14744869-Animals,
pubmed-meshheading:14744869-Binding, Competitive,
pubmed-meshheading:14744869-Binding Sites,
pubmed-meshheading:14744869-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:14744869-Cell Line,
pubmed-meshheading:14744869-Chromatin,
pubmed-meshheading:14744869-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:14744869-DNA, Complementary,
pubmed-meshheading:14744869-DNA-Binding Proteins,
pubmed-meshheading:14744869-Dose-Response Relationship, Drug,
pubmed-meshheading:14744869-Genes, Dominant,
pubmed-meshheading:14744869-Genes, Reporter,
pubmed-meshheading:14744869-Genetic Vectors,
pubmed-meshheading:14744869-Glutathione Peroxidase,
pubmed-meshheading:14744869-Humans,
pubmed-meshheading:14744869-Lipoproteins, LDL,
pubmed-meshheading:14744869-Liver,
pubmed-meshheading:14744869-Luciferases,
pubmed-meshheading:14744869-Models, Genetic,
pubmed-meshheading:14744869-Mutagenesis, Site-Directed,
pubmed-meshheading:14744869-Mutation,
pubmed-meshheading:14744869-Phosphoenolpyruvate Carboxykinase (GTP),
pubmed-meshheading:14744869-Precipitin Tests,
pubmed-meshheading:14744869-Promoter Regions, Genetic,
pubmed-meshheading:14744869-Protein Binding,
pubmed-meshheading:14744869-Protein Isoforms,
pubmed-meshheading:14744869-Proteins,
pubmed-meshheading:14744869-Rats,
pubmed-meshheading:14744869-Recombinant Proteins,
pubmed-meshheading:14744869-Sp1 Transcription Factor,
pubmed-meshheading:14744869-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:14744869-Sterol Regulatory Element Binding Protein 2,
pubmed-meshheading:14744869-Transcription, Genetic,
pubmed-meshheading:14744869-Transcription Factors,
pubmed-meshheading:14744869-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver.
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pubmed:affiliation |
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4935, USA. kxc23@cwru.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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