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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-07-2331. This Article Full Text (PDF) All Versions of this Article: 2002-07-2331v1 101/8/3042    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gruber, F. Articles by Binder, B. R Search for Related Content PubMed PubMed Citation Articles by Gruber, F. Articles by Binder, B. R Social Bookmarking                   What's this? Submitted August 1, 2002 Accepted December 10, 2002 Direct binding of Nur77/NAK-1 to the plasminogen activator inhibitor 1 (PAI-1) promoter regulates TNF-induced PAI-1 expression Florian Gruber, Peter Hufnagl, Renate Hofer-Warbinek, Johannes A Schmid, Johannes M Breuss, Renate Huber-Beckmann, Markus Lucerna, Nikolina Papac, Hanna Harant, Ivan Lindley, Rainer deMartin, and Bernd R Binder* Department of Vascular Biology and Thrombosis Research, University of Vienna, Vienna, Austria Roche Diagnostics GmbH, Vienna, Austria Novartis Research Institute, Vienna, Austria BMT-Research, Vienna, Austria LBI for Applied Cancer Research, Vienna, Austria * Corresponding author; email: bernd.binder{at}univie.ac.at. Plasminogen activator inhibitor 1 (PAI-1) is the main fibrinolysis inhibitor and high plasma levels are associated with an increased risk for vascular diseases. Inflammatory cytokines regulate PAI-1 through a hitherto unclear mechanism. Using reporter gene analysis we could identify a region in the PAI-1 promoter that contributes to basal expression as well as to TNF induction of PAI-1 in endothelial cells. Using this region as bait in a genetic screen we could identify Nur77 (NAK-1, TR3, NR4A1) as an inducible DNA-binding protein that binds specifically to the PAI-1 promoter. Nur77 drives transcription of PAI-1 through direct binding to a NGFI-B responsive element (NBRE) indicating monomeric binding and a ligand independent mechanism. Nur77 itself is transcriptionally upregulated by TNF. High expression levels of Nur77 and its co-localization with PAI-1 in atherosclerotic tissues indicate that the described mechanism for PAI-1 regulation may also be operative in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Platzer, S. Richter, D. Kneidinger, D. Waltenberger, M. Woisetschlager, and H. 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