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Endostatin is a potential inhibitor of Wnt signaling
Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis dupli...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173844/ https://www.ncbi.nlm.nih.gov/pubmed/12147676 http://dx.doi.org/10.1083/jcb.200203064 |
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author | Hanai, Jun-ichi Gloy, Joachim Karumanchi, S. Ananth Kale, Sujata Tang, Jian Hu, Guang Chan, Barden Ramchandran, Ramani Jha, Vivek Sukhatme, Vikas P. Sokol, Sergei |
author_facet | Hanai, Jun-ichi Gloy, Joachim Karumanchi, S. Ananth Kale, Sujata Tang, Jian Hu, Guang Chan, Barden Ramchandran, Ramani Jha, Vivek Sukhatme, Vikas P. Sokol, Sergei |
author_sort | Hanai, Jun-ichi |
collection | PubMed |
description | Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by β-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and “stabilized” forms of β-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting β-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell–specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of β-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on β-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote β-catenin degradation. |
format | Text |
id | pubmed-2173844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21738442008-05-01 Endostatin is a potential inhibitor of Wnt signaling Hanai, Jun-ichi Gloy, Joachim Karumanchi, S. Ananth Kale, Sujata Tang, Jian Hu, Guang Chan, Barden Ramchandran, Ramani Jha, Vivek Sukhatme, Vikas P. Sokol, Sergei J Cell Biol Article Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by β-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and “stabilized” forms of β-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting β-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell–specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of β-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on β-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote β-catenin degradation. The Rockefeller University Press 2002-08-05 /pmc/articles/PMC2173844/ /pubmed/12147676 http://dx.doi.org/10.1083/jcb.200203064 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Hanai, Jun-ichi Gloy, Joachim Karumanchi, S. Ananth Kale, Sujata Tang, Jian Hu, Guang Chan, Barden Ramchandran, Ramani Jha, Vivek Sukhatme, Vikas P. Sokol, Sergei Endostatin is a potential inhibitor of Wnt signaling |
title | Endostatin is a potential inhibitor of Wnt signaling |
title_full | Endostatin is a potential inhibitor of Wnt signaling |
title_fullStr | Endostatin is a potential inhibitor of Wnt signaling |
title_full_unstemmed | Endostatin is a potential inhibitor of Wnt signaling |
title_short | Endostatin is a potential inhibitor of Wnt signaling |
title_sort | endostatin is a potential inhibitor of wnt signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173844/ https://www.ncbi.nlm.nih.gov/pubmed/12147676 http://dx.doi.org/10.1083/jcb.200203064 |
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