{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:10:08Z","timestamp":1789949408186,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,6,7]],"date-time":"2001-06-07T00:00:00Z","timestamp":991872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Furin is recognized as being one of the main convertases of the cellular constitutive secretion pathway but the mechanisms regulating its expression are still unknown. We have previously demonstrated that TGF\u03b21 up\u2010regulates its own converting enzyme, furin, creating a novel activation\/regulation cycle of potential importance in a variety of physiological and pathophysiological conditions. The <jats:italic>fur<\/jats:italic> (fes upstream region) gene is regulated via three alternative promoters; P1, P1A, and P1B. To gain insight into the molecular mechanism(s) underlying this up\u2010regulation, we performed transient cell transfections with P1, P1A, and P1B promoter luciferase constructs. Transfection experiments in HepG2 cells revealed that <jats:italic>fur<\/jats:italic> P1 promoter is the strongest and the most sensitive to TGF\u03b21 stimulation (5 ng\/ml) (3.2\u2010fold vs. 2.4\u2010fold for P1A and 2.1\u2010fold for P1B). Cotransfection with either a dominant negative mutant form of Smad2 [Smad2(3SA)] or a known Smad inhibitor [Smad7] inhibit constitutive and TGF\u03b21\u2010induced luciferase activity indicating the participation of endogenous Smads. Increased levels of TGF\u03b21\u2010induced transcriptional activation of the P1 promoter by overexpression of Smad2 and\/or Smad4 is greatly reduced in the presence of Smad2(3SA) and completely inhibited by Smad7, suggesting the participation of endogenous Smad2\/Smad4 complexes. Furthermore, the fork\u2010head activin signal transducer (FAST\u20101), known to interact with Smad2\/Smad4 complexes, is a potent stimulator of TGF\u03b21\u2010induced transactivation of the <jats:italic>fur<\/jats:italic> P1 promoter. Five prime\u2010deletion analysis of this promoter identified the proximal region (between positions \u22128734 and \u22127925), as the nucleotide stretch that carries most of the transcriptional activation of <jats:italic>fur<\/jats:italic> P1 promoter by Smad2. Overall, the present data demonstrate that Smad2 and Smad4 possibly in complex with FAST\u20101 or other DNA binding partners participate in the constitutive and inducible transactivation of the <jats:italic>fur<\/jats:italic> P1 promoter. This represents the first detailed study of the transcriptional regulation of the <jats:italic>fur<\/jats:italic> gene. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.1116","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:43:33Z","timestamp":1030311813000},"page":"264-273","source":"Crossref","is-referenced-by-count":49,"title":["Involvement of Smads in TGF\u03b21\u2010induced furin (<i>fur<\/i>) 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