Document Detail

Synergistic transcriptional activation of the tissue inhibitor of metalloproteinases-1 promoter via functional interaction of AP-1 and Ets-1 transcription factors.
MedLine Citation:
PMID:  8557686     Owner:  NLM     Status:  MEDLINE    
The tissue inhibitor of metalloproteinases-1 (TIMP-1) is an inhibitor of the extracellular matrix-degrading metalloproteinases. We characterized response elements that control TIMP-1 gene expression. One contains a binding site that selectively binds c-Fos and c-Jun in vitro and confers a response to multiple AP-1 family members in vivo. Adjacent to this is a binding site for Ets domain proteins. Although c-Ets-1 alone did not activate transcription from this element, it enhanced transcription synergistically with AP-1 either in the context of the natural promoter or when the sequence was linked upstream of a heterologous promoter. Furthermore, a complex of c-Jun and c-Fos interacted with c-Ets-1 in vitro. These results suggest that AP-1 tethers c-Ets-1 to the TIMP-1 promoter via protein-protein interaction to achieve Ets-dependent transcriptional regulation. Collectively, our results indicate that TIMP-1 expression is controlled by several DNA response elements that respond to variations in the level and activity of AP-1 and Ets transcriptional regulatory proteins.
S K Logan; M J Garabedian; C E Campbell; Z Werb
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-02-26     Completed Date:  1996-02-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  774-82     Citation Subset:  IM    
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143, USA.
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MeSH Terms
Base Sequence
Glycoproteins / genetics*,  metabolism
Molecular Sequence Data
Promoter Regions, Genetic / genetics
Proto-Oncogene Protein c-ets-1
Proto-Oncogene Proteins / genetics*,  metabolism
Proto-Oncogene Proteins c-ets
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
Tissue Inhibitor of Metalloproteinases
Transcription Factor AP-1 / genetics*,  metabolism
Transcription Factors / genetics*,  metabolism
Transcriptional Activation*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Ets1 protein, mouse; 0/Glycoproteins; 0/Proto-Oncogene Protein c-ets-1; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-ets; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Tissue Inhibitor of Metalloproteinases; 0/Transcription Factor AP-1; 0/Transcription Factors

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