| Ectopic expression of the cAMP-responsive element binding protein inhibits phorbol ester-mediated induction of tissue-type plasminogen activator gene expression. | |
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MedLine Citation:
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PMID: 11179965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The human tissue-type plasminogen activator (t-PA) gene is regulated in a cell-type dependent manner. The t-PA gene is transcriptionally induced by the phorbol ester PMA in HeLa cells, but suppressed by PMA in HT-1080 cells. A cAMP responsive element (tPACRE) and a Sp-1 site located within the proximal t-PA gene promoter are functionally important in both cell systems. HeLa and HT-1080 cells contain a different repertoire of factors that associate with the tPACRE. In HT-1080 cells, CREB and c-Jun are the two major t-PACRE binding proteins identified, while activating transcription factor 2 (ATF-2) is a predominant t-PACRE binding protein in HeLa cells. To determine whether alteration in the distribution of tPACRE binding proteins would influence the differential regulation of the t-PA gene in these cells, the tPACRE binding profiles in these two cell systems were manipulated by over expressing ATF-2 in HT-1080 cells and CREB in HeLa cells. Supershift experiments confirmed that the overexpression of these factors resulted in binding to the tPACRE site. However, the presence of ATF-2 in HT-1080 cells did not affect either constitutive or PMA-mediated suppression of the endogenous t-PA gene. In contrast, enforced tPACRE-binding activity of CREB in HeLa cells significantly reduced the magnitude of PMA-mediated induction of t-PA mRNA in HeLa cells. These results indicate that the introduction of CREB into HeLa cells disrupts the regulation of the t-PA gene. |
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Authors:
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M Costa; R L Medcalf |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 268 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-04-05 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: Germany |
Other Details:
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Languages: eng Pagination: 987-96 Citation Subset: IM |
Affiliation:
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Monash University Department of Medicine, Box Hill Hospital, Box Hill, Victoria, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Activating Transcription Factor 2 Cyclic AMP Response Element Modulator Cyclic AMP Response Element-Binding Protein / genetics, metabolism, physiology* DNA-Binding Proteins / metabolism Gene Silencing* Hela Cells Humans Phorbol Esters / pharmacology* Repressor Proteins / metabolism Response Elements Tissue Plasminogen Activator / genetics*, metabolism Transcription Factors / genetics, metabolism Transcriptional Activation Transfection |
| Chemical | |
Reg. No./Substance:
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0/ATF2 protein, human; 0/Activating Transcription Factor 2; 0/Cyclic AMP Response Element-Binding Protein; 0/DNA-Binding Proteins; 0/Phorbol Esters; 0/Repressor Proteins; 0/Transcription Factors; 135844-64-3/Cyclic AMP Response Element Modulator; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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