PloS one, 2011-04, Vol.6 (4), p.e19185-e19185
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Discovery of novel small molecule activators of β-catenin signaling
- Ist Teil von
- PloS one, 2011-04, Vol.6 (4), p.e19185-e19185
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0019185Titel-ID: cdi_plos_journals_1296873661
- Format
- –
- Schlagworte
- Aberration, Animals, beta Catenin - metabolism, beta-Galactosidase - metabolism, Biocompatibility, Biology, Biomedical materials, Bone growth, Cell activation, Cell growth, Cell Line, Cell Line, Tumor, Cell lines, Chemistry, CHO Cells, Complementation, Cricetinae, Cricetulus, Cytoplasm - metabolism, Drug Design, Embryogenesis, Embryonic growth stage, Enzymes, Frizzled protein, Galactosidase, Glycogen, Glycogen synthase kinase 3, Glycogen Synthase Kinases - metabolism, Growth factors, HeLa Cells, Humans, Kinases, Laboratories, Machinery, Machinery and equipment, Medicine, Models, Biological, Neurodegenerative diseases, Osteogenesis, Osteosarcoma, Peptides, Pharmacology, Protein Binding, Proteins, Receptors, Regulation, Reporter gene, Selectivity, Signal Transduction, Signaling, Stem cells, Toxicology, Wnt protein, β-Catenin, β-Galactosidase