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14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β
BACKGROUND: Pluripotent embryonic stem cells are considered to be an unlimited cell source for tissue regeneration and cell-based therapy. Investigating the molecular mechanism underlying the regulation of embryonic stem cell expansion is thus important. 14-3-3 proteins are implicated in controlling...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387134/ https://www.ncbi.nlm.nih.gov/pubmed/22768254 http://dx.doi.org/10.1371/journal.pone.0040193 |
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author | Chang, Tzu-Ching Liu, Chia-Chia Hsing, En-Wei Liang, Shu-Man Chi, Ya-Hui Sung, Li-Ying Lin, Shau-Ping Shen, Tang-Long Ko, Bor-Sheng Yen, B. Linju Yet, Shaw-Fang Wu, Kenneth K. Liou, Jun-Yang |
author_facet | Chang, Tzu-Ching Liu, Chia-Chia Hsing, En-Wei Liang, Shu-Man Chi, Ya-Hui Sung, Li-Ying Lin, Shau-Ping Shen, Tang-Long Ko, Bor-Sheng Yen, B. Linju Yet, Shaw-Fang Wu, Kenneth K. Liou, Jun-Yang |
author_sort | Chang, Tzu-Ching |
collection | PubMed |
description | BACKGROUND: Pluripotent embryonic stem cells are considered to be an unlimited cell source for tissue regeneration and cell-based therapy. Investigating the molecular mechanism underlying the regulation of embryonic stem cell expansion is thus important. 14-3-3 proteins are implicated in controlling cell division, signaling transduction and survival by interacting with various regulatory proteins. However, the function of 14-3-3 in embryonic stem cell proliferation remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we show that all seven 14-3-3 isoforms were detected in mouse embryonic stem cells. Retinoid acid suppressed selectively the expression of 14-3-3σ isoform. Knockdown of 14-3-3σ with siRNA reduced embryonic stem cell proliferation, while only 14-3-3σ transfection increased cell growth and partially rescued retinoid acid-induced growth arrest. Since the growth-enhancing action of 14-3-3σ was abrogated by β-catenin knockdown, we investigated the influence of 14-3-3σ overexpression on β-catenin/GSK-3β. 14-3-3σ bound GSK-3β and increased GSK-3β phosphorylation in a PI-3K/Akt-dependent manner. It disrupted β-catenin binding by the multiprotein destruction complex. 14-3-3σ overexpression attenuated β-catenin phosphorylation and rescued the decline of β-catenin induced by retinoid acid. Furthermore, 14-3-3σ enhanced Wnt3a-induced β-catenin level and GSK-3β phosphorylation. DKK, an inhibitor of Wnt signaling, abolished Wnt3a-induced effect but did not interfere GSK-3β/14-3-3σ binding. SIGNIFICANCE: Our findings show for the first time that 14-3-3σ plays an important role in regulating mouse embryonic stem cell proliferation by binding and sequestering phosphorylated GSK-3β and enhancing Wnt-signaled GSK-3β inactivation. 14-3-3σ is a novel target for embryonic stem cell expansion. |
format | Online Article Text |
id | pubmed-3387134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33871342012-07-05 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β Chang, Tzu-Ching Liu, Chia-Chia Hsing, En-Wei Liang, Shu-Man Chi, Ya-Hui Sung, Li-Ying Lin, Shau-Ping Shen, Tang-Long Ko, Bor-Sheng Yen, B. Linju Yet, Shaw-Fang Wu, Kenneth K. Liou, Jun-Yang PLoS One Research Article BACKGROUND: Pluripotent embryonic stem cells are considered to be an unlimited cell source for tissue regeneration and cell-based therapy. Investigating the molecular mechanism underlying the regulation of embryonic stem cell expansion is thus important. 14-3-3 proteins are implicated in controlling cell division, signaling transduction and survival by interacting with various regulatory proteins. However, the function of 14-3-3 in embryonic stem cell proliferation remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we show that all seven 14-3-3 isoforms were detected in mouse embryonic stem cells. Retinoid acid suppressed selectively the expression of 14-3-3σ isoform. Knockdown of 14-3-3σ with siRNA reduced embryonic stem cell proliferation, while only 14-3-3σ transfection increased cell growth and partially rescued retinoid acid-induced growth arrest. Since the growth-enhancing action of 14-3-3σ was abrogated by β-catenin knockdown, we investigated the influence of 14-3-3σ overexpression on β-catenin/GSK-3β. 14-3-3σ bound GSK-3β and increased GSK-3β phosphorylation in a PI-3K/Akt-dependent manner. It disrupted β-catenin binding by the multiprotein destruction complex. 14-3-3σ overexpression attenuated β-catenin phosphorylation and rescued the decline of β-catenin induced by retinoid acid. Furthermore, 14-3-3σ enhanced Wnt3a-induced β-catenin level and GSK-3β phosphorylation. DKK, an inhibitor of Wnt signaling, abolished Wnt3a-induced effect but did not interfere GSK-3β/14-3-3σ binding. SIGNIFICANCE: Our findings show for the first time that 14-3-3σ plays an important role in regulating mouse embryonic stem cell proliferation by binding and sequestering phosphorylated GSK-3β and enhancing Wnt-signaled GSK-3β inactivation. 14-3-3σ is a novel target for embryonic stem cell expansion. Public Library of Science 2012-06-29 /pmc/articles/PMC3387134/ /pubmed/22768254 http://dx.doi.org/10.1371/journal.pone.0040193 Text en Chang 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 Chang, Tzu-Ching Liu, Chia-Chia Hsing, En-Wei Liang, Shu-Man Chi, Ya-Hui Sung, Li-Ying Lin, Shau-Ping Shen, Tang-Long Ko, Bor-Sheng Yen, B. Linju Yet, Shaw-Fang Wu, Kenneth K. Liou, Jun-Yang 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title_full | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title_fullStr | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title_full_unstemmed | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title_short | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
title_sort | 14-3-3σ regulates β-catenin-mediated mouse embryonic stem cell proliferation by sequestering gsk-3β |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387134/ https://www.ncbi.nlm.nih.gov/pubmed/22768254 http://dx.doi.org/10.1371/journal.pone.0040193 |
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