Wnt4 inhibits β-catenin/TCF signalling by redirecting β-catenin to the cell membrane
Wnt4 inhibits β-catenin/TCF signalling by redirecting β-catenin to the cell membrane
复制标题
DOI：
10.1042/bc20070072
复制
发表时间：
2008-03-01
影响因子：
2.7
通讯作者：
Vilain, Eric
中科院分区：
文献类型：
--
作者：
Bernard, Pascal;Fleming, Alice;Vilain, Eric
背景信息。在胚胎发育过程中，β-连环蛋白对于 Wnt [无翅型 MMTV（鼠乳腺肿瘤病毒）整合位点家族] 靶基因的转录激活以及作为细胞与细胞粘附的介质都至关重要。调节其水平和亚细胞定位的信号至关重要。 Wnt 信号传导的一种机制导致 β-连环蛋白稳定，从而导致其易位到细胞核中，与 TCF（T 细胞因子，HMG 盒）相互作用并激活靶基因的转录。不太了解的是 Wnt 信号转导机制不涉及 β-连环蛋白稳定并导致 β-连环蛋白介导的转录受到抑制。结果。在这里，我们证明 Wnt 蛋白家族的成员 Wnt4（Wnt，成员 4）调节 β-连环蛋白的亚细胞定位，将其重定向到细胞膜。这种作用在 Wnt 中是独一无二的，它不会影响 β-catenin 的稳定性，但会阻止其参与 TCF 基因反式激活。结论。这种新机制表明 Wnt4 充当 β-连环蛋白功能（转录激活和细胞间粘附）两种模式之间的开关。
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.