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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
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.
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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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