Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-beta.
Biochem Biophys Res Commun
; 345(2): 595-601, 2006 Jun 30.
Article
in En
| MEDLINE
| ID: mdl-16690027
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Extracellular Matrix Proteins
/
Transforming Growth Factor beta
/
Promoter Regions, Genetic
/
Gene Silencing
/
Receptor, Fibroblast Growth Factor, Type 1
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2006
Type:
Article
Affiliation country:
United States