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

被引:70
作者
Bernard, Pascal [1 ]
Fleming, Alice [2 ,3 ]
Lacombe, Arnaud [2 ,3 ]
Harley, Vincent R. [1 ]
Vilain, Eric [2 ,3 ]
机构
[1] Monash Med Ctr, Prince Henrys Inst Med Res, Human Mol Genet Lab, Clayton, Vic 3168, Australia
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA
关键词
beta-catenin; murine-mammary-tumour virus (MMTV); subcellular localization; T-cell factor (TCF); wingless-type MMTV integration site family; member 4 (Wnt4);
D O I
10.1042/BC20070072
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background information. During embryonic development, beta-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 beta-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 beta-catenin stabilization and result in inhibition of beta-cateninmediated transcription. Results. Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of beta-catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of beta-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 beta-catenin function, transcriptional activation and cell-cell adhesion.
引用
收藏
页码:167 / 177
页数:11
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