English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency and aberrant control of β-catenin leads to failure of exit from pluripotency and lineage commitments. Hence, maintaining the appropriate level of β-catenin is important for the decision to commit to the appropriate lineage. However, how β-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 β-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 β-catenin with regard to ESC pluripotency remains elusive. Here, we demonstrate that C-terminal-binding protein 2 (Ctbp2) associates with major components of the β-catenin destruction complex and limits the accessibility of β-catenin to core transcription factors in undifferentiated ESCs. Ctbp2 knockdown leads to stabilization of β-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 β-catenin, along with priming its position on core pluripotency genes to hinder β-catenin deposition, which is central to commitment to the appropriate lineage.

Ctbp2-mediated β-catenin regulation is required for exit from pluripotency