FURIN gene transcription is stimulated by SMAD2/SMAD3:SMAD4

Stable Identifier
R-HSA-9733203
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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FURIN gene transcription is stimulated by SMAD2/SMAD3:SMAD4
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TGFB1 increases the expression of furin in rat synoviocytes (Blanchette et al. 1997). TGFB1 and TGFB2 increase the expression of FURIN in human bronchial epithelial cells (O'Sullivan et al. 2021). FURIN gene (also known as Fur, for fes upstream region) is regulated via three alternative promoters, P1, P1A and P1B. All three promoters are responsive to stimulation with TGFB1 in a SMAD2- and SMAD4-dependent manner, with the P1 promoter being the most sensitive (Blanchette et al. 2001). There exists differential accumulation of FURIN mRNA to TGFβ1 in different cell types, with some cell types (e.g., HepG2) responding better than others. The role of SMAD2 and SMAD3 also seems to be cell type-dependent, because in ovarian granulosa-lutein cells FURIN expression is dependent on SMAD3 but not on SMAD2 (Yin et al. 2020). Direct binding of SMADs to the FURIN promoter has not been demonstrated, although SMAD response elements are present (Blanchette et al. 2001).
Literature References
PubMed ID Title Journal Year
31936902 TGF-β1 Increases GDNF Production by Upregulating the Expression of GDNF and Furin in Human Granulosa-Lutein Cells

Yin, J, Chang, HM, Yi, Y, Yao, Y, Leung, PCK

Cells 2020
11424093 Involvement of Smads in TGFbeta1-induced furin (fur) transcription

Blanchette, F, Rudd, P, Grondin, F, Attisano, L, Dubois, CM

J Cell Physiol 2001
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Output
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as an event of
This event is regulated
Positively by
Regulator
p-2S-SMAD2,3:SMAD4 [nucleoplasm] (Homo sapiens)
Active Unit
p-2S-SMAD2,3:SMAD4 [nucleoplasm]
Authored
Orlic-Milacic, M  (2021-06-01)
Reviewed
Contreras, O  (2022-05-02)
Created
Orlic-Milacic, M  (2021-06-01)
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