Reactome: A Curated Pathway Database

WWTR1:SMAD stimulates transcription of SERPINE1 while TGIF:SMAD and SMAD7 inhibit it (R-HSA-2106586)

Species Homo sapiens


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).

Locations in the PathwayBrowser
Additional Information
Compartment extracellular region , nucleoplasm
Components of this entry
Input entries
Output entries
This entry is regulated by
Regulation type Name