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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2003-3-31
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 1 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/High Mobility Group Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lef1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lef1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Osteocalcin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11937-44
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12551949-3T3 Cells,
pubmed-meshheading:12551949-Animals,
pubmed-meshheading:12551949-Binding Sites,
pubmed-meshheading:12551949-Cell Differentiation,
pubmed-meshheading:12551949-Cell Division,
pubmed-meshheading:12551949-Core Binding Factor Alpha 1 Subunit,
pubmed-meshheading:12551949-Cytoskeletal Proteins,
pubmed-meshheading:12551949-DNA-Binding Proteins,
pubmed-meshheading:12551949-High Mobility Group Proteins,
pubmed-meshheading:12551949-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:12551949-Mice,
pubmed-meshheading:12551949-Mice, Inbred C3H,
pubmed-meshheading:12551949-Neoplasm Proteins,
pubmed-meshheading:12551949-Osteoblasts,
pubmed-meshheading:12551949-Osteocalcin,
pubmed-meshheading:12551949-Osteosarcoma,
pubmed-meshheading:12551949-Promoter Regions, Genetic,
pubmed-meshheading:12551949-Protein Structure, Tertiary,
pubmed-meshheading:12551949-Proto-Oncogene Proteins,
pubmed-meshheading:12551949-Rats,
pubmed-meshheading:12551949-Stem Cells,
pubmed-meshheading:12551949-Trans-Activators,
pubmed-meshheading:12551949-Transcription Factors,
pubmed-meshheading:12551949-Transcriptional Activation,
pubmed-meshheading:12551949-Tumor Cells, Cultured,
pubmed-meshheading:12551949-Wnt Proteins,
pubmed-meshheading:12551949-Zebrafish Proteins,
pubmed-meshheading:12551949-beta Catenin
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pubmed:year |
2003
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pubmed:articleTitle |
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
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pubmed:affiliation |
University of Minnesota Cancer Center, Department of Orthopaedic Surgery and Graduate Program in Microbiology, Immunology and Cancer Biology, Minneapolis, Minnesota 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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