Xx. Hua et al., Synergism between transcription factors TFE3 and Smad3 in transforming growth factor-beta-induced transcription of the Smad7 gene, J BIOL CHEM, 275(43), 2000, pp. 33205-33208
Activation of transforming growth factor-beta (TGF-beta) receptors triggers
phosphorylation of Smad2 and Smad3. After binding to Smad4, the complex en
ters the nucleus and interacts with other transcription factors to activate
gene transcription. Unlike other Smads, Smad7 inhibits phosphorylation of
Smad2 and Smad3, and its transcription is induced by TGF-beta, suggesting a
negative feedback loop. Here, we show that TFE3 and Smad3 synergistically
mediate TGF-beta -induced transcription from the Smad7 promoter by binding
to an E-box and two adjacent Smad binding elements (SBEs ), respectively. A
precise 3-base pair spacer between one SEE and the E-box is essential. Pre
viously, me showed that a similar arrangement between a SEE and an E-box of
an element is essential for TGF-beta -dependent transcription of the plasm
inogen activator inhibitor-1 gene (PAI-1) and that TGF-beta -induced phosph
orylation of Smad3 triggers its association with TFE3. Thus, TFE3-Smad3 res
ponse elements may represent a common target for TGF-beta -induced gene exp
ression.