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

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R-HSA-2106586
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Reaction [omitted]
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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
17438144 Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation

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

Mol. Cell. Biol. 2007
10199400 A Smad transcriptional corepressor

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

Cell 1999
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

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

Nat Cell Biol 2008
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