WWTR1:SMAD stimulates transcription of SERPINE1 while TGIF:SMAD and SMAD7 inhibit it

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Reaction [omitted]
Homo sapiens
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Knocking down WWTR1 (TAZ) expression by siRNA treatment inhibits TGF-beta-dependent transcription of SERPINE1 (PAI-1 i.e. plasminogen activator inhibitor 1) in hepatocellular carcinoma cell line Hep G2. Chromatin immunoprecipitation (ChIP) confirmed binding of both WWTR1 and SMAD2/3 to the promoter of SERPINE1 gene in response to TGF-beta stimulation (Varelas et al. 2008). Binding of TGIF1 or TGIF2 to SMAD2,3:SMAD4 heterotrimer negatively regulates transcription of SERPINE1 (Wotton et al. 1999, Melhuish et al. 2001). SMAD7 can also bind PAI-1 promoter (and probably other TGF-beta-responsive promoters) and inhibit PAI-1 expression, probably by competing with SMAD2,3:SMAD4 binding (Zhang et al. 2007).
Literature References
PubMed ID Title Journal Year
10199400 A Smad transcriptional corepressor

Massague, J, Lee, S, Lo, RS, Wotton, D

Cell 1999
17438144 Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation

Zhang, L, Feng, XH, Chen, YG, Zhang, S, Ning, Y, Zhang, R, Fei, T, Chen, F, Meng, A, Han, Y

Mol. Cell. Biol. 2007
11427533 TGIF2 interacts with histone deacetylase 1 and represses transcription

Melhuish, TA, Gallo, CM, Wotton, D

J Biol Chem 2001
18568018 TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal

Wrana, JL, Peerani, R, Rao, BM, Samavarchi-Tehrani, P, Sakuma, R, Zandstra, PW, Varelas, X, Yaffe, MB, Dembowy, J

Nat Cell Biol 2008
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