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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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