論文

査読有り
2017年12月

Down-regulation of the Wnt/beta-catenin signaling pathway by Cacnb4

MOLECULAR BIOLOGY OF THE CELL
  • Mohamad Rima
  • Marwa Daghsni
  • Anais Lopez
  • Ziad Fajloun
  • Lydie Lefrancois
  • Mireia Dunach
  • Yasuo Mori
  • Philippe Merle
  • Juan L. Bruses
  • Michel De Waard
  • Michel Ronjat
  • 全て表示

28
25
開始ページ
3699
終了ページ
3708
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1091/mbc.E17-01-0076
出版者・発行元
AMER SOC CELL BIOLOGY

The beta(4) isoform of the beta-subunits of voltage-gated calcium channel regulates cell proliferation and cell cycle progression. Herein we show that coexpression of the beta(4)-subunit with actors of the canonical Wnt/beta-catenin signaling pathway in a hepatoma cell line inhibits Wnt-responsive gene transcription and decreases cell division, in agreement with the role of the Wnt pathway in cell proliferation. beta(4)-subunit-mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of glycogen synthase kinase (GSK3) that promotes beta-catenin translocation to the nucleus. Expression of beta(4)-subunit mutants that lost the ability to translocate to the nucleus has no effect on Wnt signaling, suggesting that beta(4)-subunit inhibition of Wnt signaling occurs downstream from GSK3 and requires targeting of beta(4)-subunit to the nucleus. beta(4)-subunit coimmunoprecipitates with the TCF4 transcription factor and overexpression of TCF4 reverses the effect of beta(4)-subunit on the Wnt pathway. We thus propose that the interaction of nuclear beta(4)-subunit with TCF4 prevents beta-catenin binding to TCF4 and leads to the inhibition of the Wnt-responsive gene transcription. Thereby, our results show that beta(4)-subunit is a TCF4 repressor and therefore appears as an interesting candidate for the regulation of this pathway in neurons where beta(4)-subunit is specifically expressed.

リンク情報
DOI
https://doi.org/10.1091/mbc.E17-01-0076
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000416513200013&DestApp=WOS_CPL
ID情報
  • DOI : 10.1091/mbc.E17-01-0076
  • ISSN : 1059-1524
  • eISSN : 1939-4586
  • Web of Science ID : WOS:000416513200013

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