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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 |
2001-1-26
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pubmed:abstractText |
The steroidogenic acute regulatory protein (StAR) gene controls the rate-limiting step in the biogenesis of steroid hormones, delivery of cholesterol to the cholesterol side-chain cleavage enzyme on the inner mitochondrial membrane. We determined whether the human StAR promoter is responsive to sterol regulatory element-binding proteins (SREBPs). Expression of SREBP-1a stimulated StAR promoter activity in the context of COS-1 cells and human granulosa-lutein cells. In contrast, expression of SREBP-2 produced only a modest stimulation of StAR promoter activity. One of the SREBP-1a response elements in the StAR promoter was mapped in deletion constructs and by site-directed mutagenesis between nucleotides -81 to -70 from the transcription start site. This motif bound recombinant SREBPs in electrophoretic mobility shift assays, but with lesser affinity than a low density lipoprotein receptor SREBP-binding site. An additional binding site for the transcriptional modulator, yin yang 1 (YY1), was observed within the SREBP-binding site (nucleotides -73 to -70). Mutation of the YY1-binding site increased the responsiveness of the StAR promoter to exogenous SREBP-1a, but did not alter the affinity for SREBP-1a binding in electrophoretic mobility gel shift assays. Manipulations that altered endogenous mature SREBP-1a levels (e.g. culture in lipoprotein-deficient medium and addition of 27-hydroxycholesterol) did not affect StAR promoter function, but influenced low density lipoprotein receptor promoter activity. We conclude that 1) the human StAR promoter is conditionally responsive to SREBP-1a such that promoter activity is up-regulated in the presence of high levels of SREBP-1a, but is unaffected when mature SREBP levels are suppressed; and 2) the human StAR promoter is selectively responsive to SREBP-1a.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
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/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/steroidogenic acute regulatory...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
142
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28-36
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11145563-Animals,
pubmed-meshheading:11145563-Base Sequence,
pubmed-meshheading:11145563-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:11145563-COS Cells,
pubmed-meshheading:11145563-Cattle,
pubmed-meshheading:11145563-Cercopithecus aethiops,
pubmed-meshheading:11145563-DNA-Binding Proteins,
pubmed-meshheading:11145563-Female,
pubmed-meshheading:11145563-Gene Expression Regulation,
pubmed-meshheading:11145563-Genes, Reporter,
pubmed-meshheading:11145563-Granulosa Cells,
pubmed-meshheading:11145563-Humans,
pubmed-meshheading:11145563-Membrane Proteins,
pubmed-meshheading:11145563-Mice,
pubmed-meshheading:11145563-Molecular Sequence Data,
pubmed-meshheading:11145563-Mutagenesis, Site-Directed,
pubmed-meshheading:11145563-Phosphoproteins,
pubmed-meshheading:11145563-Promoter Regions, Genetic,
pubmed-meshheading:11145563-Rats,
pubmed-meshheading:11145563-Receptors, LDL,
pubmed-meshheading:11145563-Recombinant Proteins,
pubmed-meshheading:11145563-Sequence Alignment,
pubmed-meshheading:11145563-Sequence Deletion,
pubmed-meshheading:11145563-Sequence Homology, Nucleic Acid,
pubmed-meshheading:11145563-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:11145563-Transcription Factors,
pubmed-meshheading:11145563-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a.
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pubmed:affiliation |
Center for Research on Reproduction and Women's Health, University of Pennsylvania (L.K.C., J.F.S.), Philadelphia, Pennsylvania 19104.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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