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Papers In Press, published online ahead of print September 5, 2000
Department of Biology, Whitehead Institute, MIT, Cambridge, MA 02142
Corresponding Author: Lodish{at}wi.mit.edu
Activation of TGF-ß receptors triggers phosphorylation of Smads 2 and 3; after binding to Smad 4 the Smad complex enters the nucleus and interacts with other transcription factors to activate gene transcription. Unlike other Smads, Smad 7 inhibits phosphorylation of Smads 2 and 3 and its transcription is induced by TGF-ß, suggesting a negative feedback loop. Here we show that TFE3 and Smad 3 synergistically mediate TGF-ß-induced transcription from the Smad 7 promoter by binding to an E-box and two adjacent Smad binding elements (SBEs), respectively. A precise 3 base pair spacer between one SBE and the E box is essential. Previously we showed that a similar arrangement between a SBE and an E-box is essential for TGF-ß-dependent transcription of the plasminogen activator inhibitor-1 gene (PAI-1), and that TGF-ß-induced phosphorylation of Smad 3 triggers its association with TFE3. Thus, TFE3-Smad3 response elements may represent a common target for TGF-ß- induced gene expression.
J. Biol. Chem, 10.1074/jbc.C000568200
Submitted on August 21, 2000
Accepted on September 5, 2000
Synergism between transcription factors TFE3 and Smad 3 in TGF-ß-induced transcription of the Smad 7 gene
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