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http://ir.nhri.org.tw/handle/3990099045/6510
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Title: | 14-3-3sigma regulates beta-catenin-mediated mouse embryonic stem cell proliferation by sequestering GSK-3beta |
Other Titles: | 14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β |
Authors: | Chang, TC;Liu, CC;Hsing, EW;Liang, SM;Chi, YH;Sung, LY;Lin, SP;Shen, TL;Ko, BS;Yen, BL;Yet, SF;Wu, KK;Liou, JY |
Contributors: | Institute of Cellular and Systems Medicine |
Abstract: | 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. |
Date: | 2012-06 |
Relation: | PLoS ONE. 2012 Jun;7(6):Article number e40193. |
Link to: | http://dx.doi.org/10.1371/journal.pone.0040193 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000305892100227 |
Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84863112758 |
Appears in Collections: | [劉俊揚] 期刊論文 [伍焜玉] 期刊論文 [顏伶汝] 期刊論文 [林秀芳] 期刊論文 [紀雅惠] 期刊論文
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