Posttranscriptional regulation of PAI-1 gene expression
Joanne H. Heaton(1),Wendy M. Dlakic(1),Thomas D. Gelehrter(1, 2)
(1)Department of Human Genetics and (2)Department of Internal Medicine, University of Michigan Medical School,Ann Arbor, Michigan, USA
Summary
SummaryThe plasminogen activator-plasmin cascade is involved inmultiple physiological and pathological processes includingfibrinolysis, wound healing, fibrosis, angiogenesis, embryo implantationand tumor cell invasion and metastasis. Plasminogenactivator-inhibitor type 1 (PAI-1) is the major physiologicalregulator of plasminogen activation. PAI-1 is expressed in avariety of mammalian cells and is regulated by growth factors,cytokines and hormones, including agents that elevate cAMPlevels. Although cyclic nucleotide regulation of PAI-1 is observed in diverse cell types in various species, including human, limitedstudies have addressed the mechanism of this regulation.Here we review our work on the regulation of PAI-1 mRNAdegradation in HTC rat hepatoma cells, describing the cis-actingcAMP-responsive sequence in the transcript and a novelRNA binding protein that interacts with it. Potential mechanismsby which this RNA-binding protein may be involved incyclic nucleotide regulation of mRNA stability are discussedand cAMP regulation of PAI-1 in other systems is summarized.