Wnt4 inhibits β-catenin/TCF signalling by redirecting β-catenin to the cell membrane

Pascal Bernard, Alice Fleming, Arnaud Lacombe, Vincent R. Harley, Eric Vilain

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66 Citations (Scopus)

Abstract

Background information. During embryonic development, β-catenin is central both to the transcriptional activation of Wnt [wingless-type MMTV (murine-mammary-tumour virus) integration site family] target genes and as a mediator of cell-cell adhesion. Signals that regulate its levels and subcellular localization are critical. One mechanism of Wnt signalling results in stabilization of β-catenin protein, which leads to its translocation into the nucleus, where it interacts with TCF (T-cell factor, HMG box) and activates transcription of target genes. Less well understood are mechanisms of Wnt signalling that do not involve β-catenin stabilization and result in inhibition of β-catenin-mediated transcription. Results. Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of β-catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of β-catenin but does prohibit its involvement in TCF gene transactivation. Conclusions. This novel mechanism suggests that Wnt4 acts as a switch between the two modes of β-catenin function, transcriptional activation and cell-cell adhesion.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalBiology of the Cell
Volume100
Issue number3
DOIs
Publication statusPublished - 1 Mar 2008
Externally publishedYes

Keywords

  • β-catenin
  • Member 4 (Wnt4)
  • Murine-mammary-tumour virus (MMTV)
  • Subcellular localization
  • T-cell factor (TCF)
  • Wingless-type MMTV integration site family

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