Source:http://linkedlifedata.com/resource/pubmed/id/12433930
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2003-1-20
|
| pubmed:abstractText |
Activation protein-1 (AP-1) transcription factors are early response genes involved in a diverse set of transcriptional regulatory processes. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is often used to induce AP-1 activity. The purpose of this work was to explore the molecular mechanisms involved in the TPA regulation of ubiquitous 5-aminolevulinate synthase (ALAS) gene expression, the first and rate-controlling step of the heme biosynthesis. Previous analysis of the 5'-flanking sequence of ALAS revealed the existence of two cAMP-response elements (CRE) required for basal and cAMP-stimulated expression. The fragment -833 to +42 in the 5'-flanking region of rat ALAS gene was subcloned into a chloramphenicol acetyltransferase (CAT) reporter vector. The expression vector pALAS/CAT produced a significant CAT activity in transiently transfected HepG2 human hepatoma cells, which was repressed by TPA. Sequence and deletion analysis detected a TPA response element (TRE), located between -261 and -255 (TRE-ALAS), that was critical for TPA regulation. We demonstrated that c-Fos, c-Jun, and JunD are involved in TPA inhibitory effect due to their ability to bind TRE-ALAS, evidenced by supershift analysis and their capacity to repress promoter activity in transfection assays. Repression of ALAS promoter activity by TPA treatment or Fos/Jun overexpression was largely relieved when CRE protein-binding protein or p300 was ectopically expressed. When the TRE site was placed in a different context with respect to CRE sites, it appeared to act as a transcriptional enhancer. We propose that the decrease in ALAS basal activity observed in the presence of TPA may reflect a lower ability of this promoter to assemble the productive pre-initiation complex due to CRE protein-binding protein sequestration. We also suggest that the transcriptional properties of this AP-1 site would depend on a spatial-disposition-dependent manner with respect to the CRE sites and to the transcription initiation site.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-Aminolevulinate Synthetase,
http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/CREBBP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/calphostin C
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
24
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2317-26
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:12433930-5-Aminolevulinate Synthetase,
pubmed-meshheading:12433930-Blotting, Western,
pubmed-meshheading:12433930-CREB-Binding Protein,
pubmed-meshheading:12433930-Cloning, Molecular,
pubmed-meshheading:12433930-Cyclic AMP,
pubmed-meshheading:12433930-Dimerization,
pubmed-meshheading:12433930-Dose-Response Relationship, Drug,
pubmed-meshheading:12433930-Gene Deletion,
pubmed-meshheading:12433930-Genes, Dominant,
pubmed-meshheading:12433930-Genes, Reporter,
pubmed-meshheading:12433930-Genetic Vectors,
pubmed-meshheading:12433930-Humans,
pubmed-meshheading:12433930-Models, Biological,
pubmed-meshheading:12433930-Mutagenesis, Site-Directed,
pubmed-meshheading:12433930-Naphthalenes,
pubmed-meshheading:12433930-Nuclear Proteins,
pubmed-meshheading:12433930-Precipitin Tests,
pubmed-meshheading:12433930-Promoter Regions, Genetic,
pubmed-meshheading:12433930-Protein Binding,
pubmed-meshheading:12433930-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:12433930-RNA, Messenger,
pubmed-meshheading:12433930-Time Factors,
pubmed-meshheading:12433930-Trans-Activators,
pubmed-meshheading:12433930-Transcription, Genetic,
pubmed-meshheading:12433930-Transcription Factor AP-1,
pubmed-meshheading:12433930-Transfection,
pubmed-meshheading:12433930-Tumor Cells, Cultured
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Inhibitory effect of AP-1 complex on 5-aminolevulinate synthase gene expression through sequestration of cAMP-response element protein (CRE)-binding protein (CBP) coactivator.
|
| pubmed:affiliation |
Laboratorio de Biologia Molecular, Departamento de Quimica Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II Piso 4, Ciudad Universitaria, Argentina.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|