WWTR1:SMAD stimulates transcription of SMAD7

Stable Identifier
R-HSA-2106591
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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WWTR1:SMAD stimulates transcription of SMAD7
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Knocking down WWTR1 (TAZ) expression by siRNA treatment inhibits TGF-beta-dependent transcription of SMAD7 in human hepatocellular carcinoma cell line Hep G2. Chromatin immunoprecipitation (ChIP) confirmed binding of both WWTR1 and SMAD2/3 to the promoter of SMAD7 gene in response to TGF-beta stimulation (Varelas et al. 2008).
In fish, amphibian and avian species, ATP1B4 (aka X,K ATPase subunit beta m) functions as a subunit of Na/K ATPase, located in the plasma membrane. In mammals, this functionality is lost and ATP1B4 accumulates on the nuclear envelope where it can interact with SNW domain containing protein 1 (SNW1 aka Ski interacting protein, SKIP), a transcriptional regulator. This ATP1B4:SNW1 complex is able to modulate TGF beta mediated transcription by increasing mRNA levels of SMAD7, an inhibitor of TGF beta signalling (Pestov et al. 2007).
Literature References
PubMed ID Title Journal Year
17592128 Evolution of Na,K-ATPase beta m-subunit into a coregulator of transcription in placental mammals

Pestov, NB, Ahmad, N, Korneenko, TV, Zhao, H, Radkov, R, Schaer, D, Roy, S, Bibert, S, Geering, K, Modyanov, NN

Proc. Natl. Acad. Sci. U.S.A. 2007
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
Positively by
Regulator
WWTR1:p-2S-SMAD2,3:SMAD4:SMAD7 gene [nucleoplasm] (Homo sapiens)
Active Unit
WWTR1:p-2S-SMAD2,3:SMAD4 [nucleoplasm]
Regulator
ATP1B4:SNW1 [nucleoplasm] (Homo sapiens)
Authored
Orlic-Milacic, M  (2012-04-05)
Reviewed
Huang, T  (2012-05-14)
Contreras, O  (2022-05-02)
Created
Orlic-Milacic, M  (2012-02-11)
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