Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1996-12-2
|
| pubmed:abstractText |
Treatment of GT1-7 neuronal cells with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), inhibits GnRH gene transcription. The present studies investigated the role of AP-1 (Fos and Jun) in this repression. Treatment of cells with TPA increased c-fos mRNA 20-fold with only a 2-fold increase in c-jun mRNA levels. In transient transfection studies, a luciferase expression vector containing fragments of the 5'-flanking DNA of the rat GnRH (rGnRH) promoter was cotransfected with Fos and Jun expression vectors to mimic the effects of TPA. A dose-dependent decrease in reporter activity was noted with increasing amounts of Fos but not with Jun overexpression. Deletion analysis mapped the region that mediates repression by AP-1 to the area between -126 and -73 base pairs (bp) of the rGnRH 5'-flanking region: the same area that mediates TPA-induced repression and contains an imperfect TPA response element sequence at -99. Gel retardation assays, however, showed that a DNA fragment from -111 to -73 of the rGnRH promoter does not directly interact with Fos in GT1-7 extracts. Coexpression of Fos proteins with mutations in the DNA-binding region, the dimerization domain, or carboxy terminus partially blocked inhibition of rGnRH promoter activity. These data support a novel mechanism of AP-1 repression of GnRH transcription that is mediated by Fos interaction with other protein(s) that directly bind to the proximal rGnRH promoter.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Gonadotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0888-8809
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
10
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
35-44
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8838143-Animals,
pubmed-meshheading:8838143-Base Sequence,
pubmed-meshheading:8838143-Binding Sites,
pubmed-meshheading:8838143-DNA,
pubmed-meshheading:8838143-Gene Expression,
pubmed-meshheading:8838143-Genes, fos,
pubmed-meshheading:8838143-Genes, jun,
pubmed-meshheading:8838143-Gonadotropin-Releasing Hormone,
pubmed-meshheading:8838143-Leucine Zippers,
pubmed-meshheading:8838143-Luciferases,
pubmed-meshheading:8838143-Molecular Sequence Data,
pubmed-meshheading:8838143-Promoter Regions, Genetic,
pubmed-meshheading:8838143-RNA, Messenger,
pubmed-meshheading:8838143-Rats,
pubmed-meshheading:8838143-Tetradecanoylphorbol Acetate,
pubmed-meshheading:8838143-Transcription, Genetic,
pubmed-meshheading:8838143-Transcription Factor AP-1,
pubmed-meshheading:8838143-Transfection
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Phorbol ester inhibition of rat gonadotropin-releasing hormone promoter activity: role of Fos and Jun in the repression of transcription.
|
| pubmed:affiliation |
Department of Medicine, University of Colorado Health Sciences Center, Denver 80220, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|