http://purl.uniprot.org/citations/12551949 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/12551949 | http://www.w3.org/2000/01/rdf-schema#comment | "Functional control of the transcription factor Runx2 is crucial for normal bone formation. Runx2 is detectable throughout osteoblast development and maturation and temporally regulates several bone-specific genes. In this study, we identified a novel post-translational mechanism regulating Runx2-dependent activation of the osteocalcin promoter. A functional binding site for the high mobility group protein lymphoid enhancer-binding factor 1 (LEF1) was found adjacent to the proximal Runx2-binding site in the osteocalcin promoter. In transcription assays, LEF1 repressed Runx2-induced activation of the mouse osteocalcin 2 promoter in several osteoblast lineage cell lines. Mutations in the LEF1-binding site increased the basal activity of the osteocalcin promoter; however, the LEF1 recognition site in the osteocalcin promoter was surprisingly not required for LEF1 repression. A novel interaction between the DNA-binding domains of Runx2 and LEF1 was identified and found crucial for LEF1-mediated repression of Runx2. LEF1 is a nuclear effector of the Wnt/LRP5/beta-catenin signaling pathway, which is also essential for osteoblast proliferation and normal skeletal development. A constitutively active beta-catenin enhanced LEF1-dependent repression of Runx2. These data identify a novel mechanism of regulating Runx2 activity in osteoblasts and link Runx2 transcriptional activity to beta-catenin signaling."xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m211443200"xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/author | "Westendorf J.J."xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/author | "Kahler R.A."xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/pages | "11937-11944"xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/title | "Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter."xsd:string |
http://purl.uniprot.org/citations/12551949 | http://purl.uniprot.org/core/volume | "278"xsd:string |
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