Document Detail


Regulation of the tissue factor promoter in endothelial cells. Binding of NF kappa B-, AP-1-, and Sp1-like transcription factors.
MedLine Citation:
PMID:  7876129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tissue factor is up-regulated on endothelial cells and monocytes in response to cytokines and endotoxin and is the main trigger of the extrinsic pathway of the coagulation cascade. We have isolated the porcine tissue factor gene and studied the regulation of the promoter, which has not been investigated previously in endothelial cells. Comparison of the promoter sequences with the respective human and murine genes reveals short stretches of homology, which encompass potential binding sites for AP-1, NF kappa B, and Sp1 transcription factors. Using DNase I footprinting, we detect binding of nuclear factors to these promoter elements. Transfection experiments demonstrate that a 300-base pair fragment containing the conserved elements can mediate induced transcription and that the NF kappa B-like element is essential. In accordance, electrophoretic mobility shift assays show a strong increase in the binding of factors to the NF kappa B-like site following induction. We further provide evidence that RelA (p65), c-Rel, and possibly novel polypeptides bind to the tissue factor NF kappa B element. In addition, we show constitutive binding of members of the Fos/Jun and Sp1 families to the AP-1 and Sp1 sites, respectively. We propose a concerted action of AP-1-, NF kappa B-, and Sp1-like factors in transcription from the tissue factor promoter in endothelial cells.
Authors:
T Moll; M Czyz; H Holzmüller; R Hofer-Warbinek; E Wagner; H Winkler; F H Bach; E Hofer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  270     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-31     Completed Date:  1995-03-31     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:  3849-57     Citation Subset:  IM    
Affiliation:
Department of Transplantation Immunology, Vienna International Research Cooperation Center, Vienna, Austria.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/Z46238
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blood Coagulation
Cells, Cultured
Endothelium, Vascular / cytology,  metabolism*
Humans
Mice
Molecular Sequence Data
NF-kappa B / metabolism*
Promoter Regions, Genetic*
Protein Binding
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-rel
Sequence Homology, Nucleic Acid
Sp1 Transcription Factor / metabolism*
Swine
Thromboplastin / genetics*,  metabolism
Transcription Factor AP-1 / metabolism*
Transcription Factor RelA
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-rel; 0/Sp1 Transcription Factor; 0/Transcription Factor AP-1; 0/Transcription Factor RelA; 9035-58-9/Thromboplastin

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


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