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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
1997-4-18
|
| pubmed:abstractText |
Steroidogenic factor-1/adrenal 4-binding protein (SF-1/Ad4BP) is an orphan nuclear receptor/transcription factor known to regulate the P450 steroid hydroxylases; however, mechanisms that regulate the activity of SF-1/Ad4BP are not well defined. In addition, little is known about the mechanisms that regulate the human steroidogenic enzyme, type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD II), the major gonadal and adrenal isoform. Regulation of the 3beta-HSD II promoter was examined using human adrenal cortical (H295R; steroidogenic) and cervical (HeLa; non-steroidogenic) carcinoma cells. H295R cells were transfected with a series of 5' deletions of 1251 base pairs (bp) of the 3beta-HSD II 5'-flanking region fused to a chloramphenicol acetyltransferase (CAT) reporter gene followed by treatment with or without phorbol ester (phorbol 12-myristate 13-acetate; PMA). CAT assay data indicated that the region from -101 to -52 bp of the promoter was required for PMA-induced expression. A putative SF-1/Ad4BP regulatory element, TCAAGGTAA, was identified by sequence homology at -64 to -56 bp of the promoter. Cotransfection of HeLa cells with the -101 3beta-HSD-CAT construct and an expression vector for SF-1/Ad4BP increased CAT activity 49-fold. Subsequent treatment with PMA induced an unexpected synergistic increase in transcriptional activity 540-fold over basal. Mutation of the putative response element (TCAAGGTAA to TCAATTTAA) abolished SF-1-induced CAT activity and the synergistic response to PMA. Gel mobility shift assays confirmed that SF-1/Ad4BP interacts with the putative element and transcripts for SF-1/Ad4BP were detected in H295R cells by Northern analysis. These data are the first to demonstrate 1) regulation of a non-cytochrome P450 steroidogenic enzyme promoter by SF-1/Ad4BP, 2) a powerful synergistic effect of PMA on SF-1/Ad4BP-induced transcription, and 3) the importance of the SF-1/Ad4BP regulatory element in the regulation of the 3beta-HSD II promoter.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3 beta-hydroxysteroid...,
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fushi Tarazu Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NR5A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Progesterone Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Isomerases,
http://linkedlifedata.com/resource/pubmed/chemical/Steroidogenic Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
21
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7960-7
|
| pubmed:dateRevised |
2009-8-12
|
| pubmed:meshHeading |
pubmed-meshheading:9065466-Adrenal Cortex,
pubmed-meshheading:9065466-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:9065466-DNA-Binding Proteins,
pubmed-meshheading:9065466-Fushi Tarazu Transcription Factors,
pubmed-meshheading:9065466-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9065466-HeLa Cells,
pubmed-meshheading:9065466-Homeodomain Proteins,
pubmed-meshheading:9065466-Humans,
pubmed-meshheading:9065466-Multienzyme Complexes,
pubmed-meshheading:9065466-Progesterone Reductase,
pubmed-meshheading:9065466-Promoter Regions, Genetic,
pubmed-meshheading:9065466-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:9065466-Steroid Isomerases,
pubmed-meshheading:9065466-Steroidogenic Factor 1,
pubmed-meshheading:9065466-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9065466-Transcription, Genetic,
pubmed-meshheading:9065466-Transcription Factors,
pubmed-meshheading:9065466-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Synergistic activation of the human type II 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase promoter by the transcription factor steroidogenic factor-1/adrenal 4-binding protein and phorbol ester.
|
| pubmed:affiliation |
Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2515, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|