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Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation

The canonical Wnt pathway plays an important role in the regulation of cell proliferation and differentiation. Activation of this signaling pathway causes disruption of the Axin/adenomatous polyposis coli/glycogen synthase kinase 3β complex, resulting in stabilization of β-catenin and its associatio...

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Detalles Bibliográficos
Autores principales: Zhang, Long, Zhou, Fangfang, van Laar, Theo, Zhang, Juan, van Dam, Hans, ten Dijke, Peter
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084683/
https://www.ncbi.nlm.nih.gov/pubmed/21411632
http://dx.doi.org/10.1091/mbc.E10-12-0985
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author Zhang, Long
Zhou, Fangfang
van Laar, Theo
Zhang, Juan
van Dam, Hans
ten Dijke, Peter
author_facet Zhang, Long
Zhou, Fangfang
van Laar, Theo
Zhang, Juan
van Dam, Hans
ten Dijke, Peter
author_sort Zhang, Long
collection PubMed
description The canonical Wnt pathway plays an important role in the regulation of cell proliferation and differentiation. Activation of this signaling pathway causes disruption of the Axin/adenomatous polyposis coli/glycogen synthase kinase 3β complex, resulting in stabilization of β-catenin and its association with lymphoid enhancer factor/T-cell factor in the nucleus. Here, we identify Fas-associated factor 1 (FAF1) as a negative regulator of Wnt/β-catenin signaling. We found overexpression of FAF1 to strongly inhibit Wnt-induced transcriptional reporter activity and to counteract Wnt-induced β-catenin accumulation. Moreover, knockdown of FAF1 resulted in an increase in β-catenin levels and in activation of Wnt/β-catenin–induced transcription. FAF1 was found to interact with β-catenin upon inhibition of proteasome. Ectopic expression of FAF1 promoted β-catenin degradation by enhancing its polyubiquitination. Functional studies in C2C12 myoblasts and KS483 preosteoblastic cells showed that FAF1 depletion resulted in activation of endogenous Wnt-induced genes and enhanced osteoblast differentiation, whereas FAF1 overexpression had the opposite effect. These results identify FAF1 as a novel inhibitory factor of canonical Wnt signaling pathway.
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spelling pubmed-30846832011-07-16 Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation Zhang, Long Zhou, Fangfang van Laar, Theo Zhang, Juan van Dam, Hans ten Dijke, Peter Mol Biol Cell Articles The canonical Wnt pathway plays an important role in the regulation of cell proliferation and differentiation. Activation of this signaling pathway causes disruption of the Axin/adenomatous polyposis coli/glycogen synthase kinase 3β complex, resulting in stabilization of β-catenin and its association with lymphoid enhancer factor/T-cell factor in the nucleus. Here, we identify Fas-associated factor 1 (FAF1) as a negative regulator of Wnt/β-catenin signaling. We found overexpression of FAF1 to strongly inhibit Wnt-induced transcriptional reporter activity and to counteract Wnt-induced β-catenin accumulation. Moreover, knockdown of FAF1 resulted in an increase in β-catenin levels and in activation of Wnt/β-catenin–induced transcription. FAF1 was found to interact with β-catenin upon inhibition of proteasome. Ectopic expression of FAF1 promoted β-catenin degradation by enhancing its polyubiquitination. Functional studies in C2C12 myoblasts and KS483 preosteoblastic cells showed that FAF1 depletion resulted in activation of endogenous Wnt-induced genes and enhanced osteoblast differentiation, whereas FAF1 overexpression had the opposite effect. These results identify FAF1 as a novel inhibitory factor of canonical Wnt signaling pathway. The American Society for Cell Biology 2011-05-01 /pmc/articles/PMC3084683/ /pubmed/21411632 http://dx.doi.org/10.1091/mbc.E10-12-0985 Text en © 2011 Zhang et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Zhang, Long
Zhou, Fangfang
van Laar, Theo
Zhang, Juan
van Dam, Hans
ten Dijke, Peter
Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title_full Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title_fullStr Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title_full_unstemmed Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title_short Fas-associated factor 1 antagonizes Wnt signaling by promoting β-catenin degradation
title_sort fas-associated factor 1 antagonizes wnt signaling by promoting β-catenin degradation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084683/
https://www.ncbi.nlm.nih.gov/pubmed/21411632
http://dx.doi.org/10.1091/mbc.E10-12-0985
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