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Molecular and Cellular Biology, December 2005, p. 10853-10862, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.10853-10862.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Ternary Complex Factor Net Regulates Cell Migration through Inhibition of PAI-1 Expression

Gilles Buchwalter, Christian Gross, and Bohdan Wasylyk^*

Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France

Received 10 June 2005/ Returned for modification 29 July 2005/ Accepted 21 September 2005

Net, Elk-1, and Sap-1 are members of the ternary complex factor (TCF) subfamily of Ets transcription factors. They form ternary complexes with serum response factor (SRF) on serum response elements of immediate early genes such as c-fos and egr-1 and mediate responses to growth factors and mitogen-activated protein kinase signaling. Although the TCFs have been extensively studied as intermediates in signaling cascades, surprisingly little is known about their different target genes and physiological functions. We report that Net homozygous mutant mouse embryonic fibroblasts have a defect in cell migration. This defect results at least in part from increased expression of plasminogen activator inhibitor type 1 (PAI-1), a serine protease inhibitor (serpin) that controls extracellular proteolysis and cell matrix adhesion. The defect in cell migration can be reverted by the addition of a PAI-1 blocking antibody. Net represses PAI-1 promoter activity and binds to a specific region of the promoter containing Ets binding sites in the absence of SRF. We conclude that Net is a negative regulator of PAI-1 expression and is thereby involved in cell migration.

G.B. and C.G. contributed equally to this work.

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