Document Detail

Ectopic expression of the cAMP-responsive element binding protein inhibits phorbol ester-mediated induction of tissue-type plasminogen activator gene expression.
MedLine Citation:
PMID:  11179965     Owner:  NLM     Status:  MEDLINE    
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.
M Costa; R L Medcalf
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  268     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  987-96     Citation Subset:  IM    
Monash University Department of Medicine, Box Hill Hospital, Box Hill, Victoria, Australia.
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MeSH Terms
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
Phorbol Esters / pharmacology*
Repressor Proteins / metabolism
Response Elements
Tissue Plasminogen Activator / genetics*,  metabolism
Transcription Factors / genetics,  metabolism
Transcriptional Activation
Reg. No./Substance:
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 Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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