Posttranscriptional regulation of PAI-1 gene expression.
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.
Heaton
Joanne H
JH
Department of Human Genetics, 4909 Buhl Bldg., Box 0618, University of Michigan Medical School, 1241 Catherine Road, Ann Arbor, MI 48109-0618, USA. heatonj@umich.edu
Dlakic
Wendy M
WM
Gelehrter
Thomas D
TD
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; D016601:RNA-Binding Proteins; D000242:Cyclic AMP