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

Stable Identifier
R-HSA-2106586
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
extracellular region, nucleoplasm
ReviewStatus
5/5
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WWTR1:SMAD stimulates transcription of SERPINE1 while TGIF:SMAD and SMAD7 inhibit it
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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

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

Cell 1999
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
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
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
p-2S-SMAD2/3:SMAD4:TGIF:HDAC1 [nucleoplasm] (Homo sapiens)
Positively by
Regulator
WWTR1:p-2S-SMAD2,3:SMAD4:SERPINE1 gene [nucleoplasm] (Homo sapiens)
Active Unit
WWTR1:p-2S-SMAD2,3:SMAD4 [nucleoplasm]
Authored
Orlic-Milacic, M  (2012-04-05)
Reviewed
Huang, T  (2012-05-14)
Chen, YG  (2012-11-14)
Contreras, O  (2022-05-02)
Created
Orlic-Milacic, M  (2012-02-11)
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