Reactome | Knocking down WWTR1 (TAZ) expression by siRNA treatment inhi...

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created	[InstanceEdit:2106595] Orlic-Milacic, M, 2012-02-10
dbId	2106594
displayName	Knocking down WWTR1 (TAZ) expression by siRNA treatment inhi...
literatureReference	[LiteratureReference:2031354] TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal [LiteratureReference:480195] TGIF2 interacts with histone deacetylase 1 and represses transcription [LiteratureReference:2186605] A Smad transcriptional corepressor [LiteratureReference:3009225] Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation
modified	[InstanceEdit:9736962] Orlic-Milacic, Marija, 2021-07-15
schemaClass	Summation
text	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).

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