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Discovery of Novel Small Molecule Activators of β-Catenin Signaling
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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084789/ https://www.ncbi.nlm.nih.gov/pubmed/21559429 http://dx.doi.org/10.1371/journal.pone.0019185 |
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author | Verkaar, Folkert van der Stelt, Mario Blankesteijn, W. Matthijs van der Doelen, Antoon A. Zaman, Guido J. R. |
author_facet | Verkaar, Folkert van der Stelt, Mario Blankesteijn, W. Matthijs van der Doelen, Antoon A. Zaman, Guido J. R. |
author_sort | Verkaar, Folkert |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3084789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30847892011-05-10 Discovery of Novel Small Molecule Activators of β-Catenin Signaling Verkaar, Folkert van der Stelt, Mario Blankesteijn, W. Matthijs van der Doelen, Antoon A. Zaman, Guido J. R. PLoS One Research Article 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. Public Library of Science 2011-04-29 /pmc/articles/PMC3084789/ /pubmed/21559429 http://dx.doi.org/10.1371/journal.pone.0019185 Text en Verkaar et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Verkaar, Folkert van der Stelt, Mario Blankesteijn, W. Matthijs van der Doelen, Antoon A. Zaman, Guido J. R. Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title | Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title_full | Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title_fullStr | Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title_full_unstemmed | Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title_short | Discovery of Novel Small Molecule Activators of β-Catenin Signaling |
title_sort | discovery of novel small molecule activators of β-catenin signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084789/ https://www.ncbi.nlm.nih.gov/pubmed/21559429 http://dx.doi.org/10.1371/journal.pone.0019185 |
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