| http://purl.uniprot.org/citations/15668231 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15668231 | http://www.w3.org/2000/01/rdf-schema#comment | "The proteoglycan versican is pro-atherogenic and central to vascular injury and repair events. We identified the signaling pathways and promoter elements involved in regulation of versican expression in vascular smooth muscle cells. Phosphatidylinositol 3-kinase inhibitor, LY294002, significantly decreased versican-luciferase (Luc) promoter activity and endogenous mRNA levels. We further examined the roles of protein kinase B and glycogen synthase kinase (GSK)-3beta, downstream effectors of phosphatidylinositol 3-kinase, in the regulation of versican transcription. Co-transfection of dominant negative and constitutively active protein kinase B constructs with a versican-Luc construct decreased and increased promoter activity, respectively. Inhibition of GSK-3beta activity by LiCl augmented accumulation of beta-catenin and caused induction of versican-Luc activity as well as versican mRNA levels. Beta-catenin has no DNA binding domain, therefore it cannot directly induce transcription of the versican promoter. Software analysis of the versican promoter revealed two potential binding sites for T-cell factors (TCFs), proteins that confer transcriptional activation of beta-catenin. Electrophoretic mobility shift and supershift assays revealed specific binding of human TCF-4 and beta-catenin to oligonucleotides corresponding to a potential TCF binding site in the versican promoter. In addition to binding assays, we directly assessed the dependence of versican promoter activity on TCF binding sites. Site-directed mutagenesis of the TCF site located -492 bp relative to the transcription start site markedly diminished versican-Luc activity. Co-transfection of TCF-4 with versican-Luc did not increase promoter activity, but addition of beta-catenin and TCF-4 significantly stimulated basal versican promoter activity. Our findings suggest that versican transcription is predominantly mediated by the GSK-3beta pathway via the beta-catenin-TCF transcription factor complex in smooth muscle cells, wherein such regulation contributes to the normal or aberrant formation of provisional matrix in vascular injury and repair events."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m411766200"xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Luo Z."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Luo H."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Rennie P.S."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "McManus B.M."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Rahmani M."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Si X."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "McDonald P.C."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Wong B.W."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Carthy J.M."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Esfandiarei M."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/author | "Read J.T."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/pages | "13019-13028"xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/title | "Regulation of the versican promoter by the beta-catenin-T-cell factor complex in vascular smooth muscle cells."xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/15668231 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15668231 |
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| http://purl.uniprot.org/uniprot/#_A0A8I6GLH5-mappedCitation-15668231 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15668231 |