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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Datta, Pran K. Blake, Michael C. Moses, Harold L. |
| Abstract | Members of the transforming growth factor-β (TGF-β) superfamily mediate a broad range of biological activities by regulating the expression of target genes. Smad proteins play a critical role in this process by binding directly to the promoter elements and/or associating with other transcription factors. TGF-β1 up-regulates several genes transcriptionally through Sp1 binding sites; however, the mechanism of TGF-β induction of gene expression through Sp1 sites is largely unknown. Here we report the identification of a novel 38-base pair TGF-β-responsive element in the human plasminogen activator inhibitor-1 (PAI-1) promoter, which contains two Sp1 binding sites, and is required for TGF-β-induced Smad-dependent transcriptional activation. Three canonical Sp1 binding sites also support strong transcriptional activation by TGF-β and Smads from a minimal heterologous promoter. TGF-β induction of PAI-1 and p21 is blocked by the Sp1 inhibitor mithramycin, implicating Sp1 in the in vivo regulation of these genes by TGF-β. We show that the association between endogenous Sp1 and Smad3 is induced by TGF-β in several cell lines; however, Smad4 shows constitutive interaction with Sp1. These data provide novel insights into the mechanism by which TGF-β up-regulates several gene expression by activating Sp1-dependent transcription through the induction of Smad/Sp1 complex formation. |
| Related Links | http://www.jbc.org/content/275/51/40014.abstract |
| Ending Page | 40019 |
| Starting Page | 40014 |
| Page Count | 6 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 51 |
| Volume Number | 275 |
| DOI | 10.1074/jbc.C000508200 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2000-12-22 |
| Access Restriction | Open |
| Subject Keyword | Extracellular matrix (ECM) Plasminogen activator inhibitor-1 (PAI-1) Transforming growth factor-β (TGF-β) Rat intestinal epithelial (RIE) Hemagglutinin (HA) Dominant negative type II receptor (DNIIR) Histone deacetylase 1 (HDAC1) MECHANISMS OF SIGNAL TRANSDUCTION |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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