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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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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. |
format | Text |
id | pubmed-3084683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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