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).
Massague, J, Lee, S, Lo, RS, Wotton, D
Zhang, L, Feng, XH, Chen, YG, Zhang, S, Ning, Y, Zhang, R, Fei, T, Chen, F, Meng, A, Han, Y
Melhuish, TA, Gallo, CM, Wotton, D
Wrana, JL, Peerani, R, Rao, BM, Samavarchi-Tehrani, P, Sakuma, R, Zandstra, PW, Varelas, X, Yaffe, MB, Dembowy, J
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