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Thromb Haemost 2003; 89(06): 959-966
DOI: 10.1055/s-0037-1613396
DOI: 10.1055/s-0037-1613396
Review Article
Posttranscriptional regulation of PAI-1 gene expression
Financial support: This work was supported by Public Health Service Grant CA22729 from the National Cancer Institute (to T.D.G.). We also acknowledge National Institutes of Health grants 5 P30 CA46592 to the University of Michigan Comprehensive Cancer Center and 5 P60 DK-20572 to the University of Michigan Diabetes Research and Training Center for support of core services.
Further Information
Publication History
Received
31 December 2002
Accepted after revision
05 March 2003
Publication Date:
08 December 2017 (online)
Summary
The plasminogen activator-plasmin cascade is involved in multiple physiological and pathological processes including fibrinolysis, wound healing, fibrosis, angiogenesis, embryo implantation and tumor cell invasion and metastasis. Plasminogen activator-inhibitor type 1 (PAI-1) is the major physiological regulator of plasminogen activation. PAI-1 is expressed in a variety of mammalian cells and is regulated by growth factors, cytokines and hormones, including agents that elevate cAMP levels. Although cyclic nucleotide regulation of PAI-1 is observed in diverse cell types in various species, including human, limited studies have addressed the mechanism of this regulation. Here we review our work on the regulation of PAI-1 mRNA degradation in HTC rat hepatoma cells, describing the cis-acting cAMP-responsive sequence in the transcript and a novel RNA binding protein that interacts with it. Potential mechanisms by which this RNA-binding protein may be involved in cyclic nucleotide regulation of mRNA stability are discussed and cAMP regulation of PAI-1 in other systems is summarized.
Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.
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