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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 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 Citation Map 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 3042-3048 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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 de Martin, and Bernd R. Binder From the Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria; Roche Diagnostics GmbH, Vienna, Austria; Novartis Research Institute, Vienna, Austria; Bio Molecular Therapeutics (BMT) Research, Vienna, Austria; and Ludwig Boltzmann Institute for Applied Cancer Research, Vienna, Austria. 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 tumor necrosis factor  (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 an NGFI-B responsive element (NBRE), indicating monomeric binding and a ligand-independent mechanism. Nur77, itself, is transcriptionally up-regulated by TNF. High expression levels of Nur77 and its colocalization with PAI-1 in atherosclerotic tissues indicate that the described mechanism for PAI-1 regulation may also be operative in vivo. © 2003 by The American Society of Hematology.   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. Strobl Aryl Hydrocarbon Receptor Activation Inhibits In Vitro Differentiation of Human Monocytes and Langerhans Dendritic Cells J. Immunol., July 1, 2009; 183(1): 66 - 74. [Abstract] [Full Text] [PDF] H. Liu, A. E Dear, L. B Knudsen, and R. W Simpson A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules J. Endocrinol., April 1, 2009; 201(1): 59 - 66. [Abstract] [Full Text] [PDF] B. You, Y.-Y. Jiang, S. Chen, G. Yan, and J. 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