KMID : 0620920170490100002
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Experimental & Molecular Medicine 2017 Volume.49 No. 10 p.2 ~ p.2
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Ctbp2-mediated ¥â-catenin regulation is required for exit from pluripotency
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Kim Tae-Wan
Kwak So-Jung Shin Ji-Hoon Kang Byung-Hee Lee Sang-Eun Suh Min-Young Kim Jae-Hwan Hwang In-Young Lee Jong-Hyuk Choi Jin-Mi Cho Eun-Jung Youn Hong-Duk
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Abstract
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The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency and aberrant control of ¥â-catenin leads to failure of exit from pluripotency and lineage commitments. Hence, maintaining the appropriate level of ¥â-catenin is important for the decision to commit to the appropriate lineage. However, how ¥â-catenin links to core transcription factors in ESCs remains elusive. C-terminal-binding protein (CtBP) in Drosophila is essential for Wnt-mediated target gene expression. In addition, Ctbp acts as an antagonist of ¥â-catenin/TCF activation in mammals. Recently, Ctbp2, a core Oct4-binding protein in ESCs, has been reported to play a key role in ESC pluripotency. However, the significance of the connection between Ctbp2 and ¥â-catenin with regard to ESC pluripotency remains elusive. Here, we demonstrate that C-terminal-binding protein 2 (Ctbp2) associates with major components of the ¥â-catenin destruction complex and limits the accessibility of ¥â-catenin to core transcription factors in undifferentiated ESCs. Ctbp2 knockdown leads to stabilization of ¥â-catenin, which then interacts with core pluripotency-maintaining factors that are occupied by Ctbp2, leading to incomplete exit from pluripotency. These findings suggest a suppressive function for Ctbp2 in reducing the protein level of ¥â-catenin, along with priming its position on core pluripotency genes to hinder ¥â-catenin deposition, which is central to commitment to the appropriate lineage.
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KEYWORD
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Embryonic stem cells, Gene silencing
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