Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-beta

Biochem Biophys Res Commun. 2006 Jun 30;345(2):595-601. doi: 10.1016/j.bbrc.2006.04.052.

Victorino R Briones ¹, Shiyou Chen, Anna Tate Riegel, Robert J Lechleider

Affiliations

Affiliation

1 Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20057, USA.

PMID: 16690027 DOI: 10.1016/j.bbrc.2006.04.052

Abstract

Transforming growth factor-beta (TGF-beta) is the prototypical member of a family of growth factors that play important roles in normal development and human diseases. We identified the gene for fibroblast growth factor-binding protein 1 (FGF-BP1) as being significantly repressed following TGF-beta treatment. FGF-BP1 is an extracellular matrix bound protein that enhances Fibroblast Growth Factor (FGF) signaling. We demonstrate here that TGF-beta signaling significantly represses FGF-BP1 expression in mesenchymal and neural crest cells undergoing in vitro smooth muscle differentiation. Analysis of the downstream signaling pathways shows that SMAD2/3 are crucial for efficient FGF-BP1 repression by TGF-beta. Furthermore, we identified a novel element in the region from -785 to -782 bp of the FGF-BP1 promoter, which represents a known binding site for Hypermethylation in Cancer-1 (Hic-1), necessary for repression of FGF-BP1 by TGF-beta. These data define the molecular mechanism of transcriptional repression of an important target of TGF-beta signaling during angiogenesis.

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