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首页> 外文期刊>Molecular and Cellular Biology >Wnt-1 regulates free pools of catenins and stabilizes APC-catenin complexes.
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Wnt-1 regulates free pools of catenins and stabilizes APC-catenin complexes.

机译：Wnt-1调节连环蛋白的自由池并稳定APC-连环蛋白复合物。

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摘要

The Wnt-1 proto-oncogene induces the accumulation of beta-catenin and plakoglobin, two related proteins that associate with and functionally modulate the cadherin cell adhesion proteins. Here we have investigated the effects of Wnt-1 expression on the tumor suppressor protein APC, which also associates with catenins. Expression of Wnt-1 in two different cell lines greatly increased the stability of APC-catenin complexes. The steady-state levels of both catenins and APC were elevated by Wnt-1, and the half-lives of both beta-catenin and plakoglobin associated with APC were also markedly increased. The stabilization of catenins by Wnt-1 was primarily the result of a selective increase in the amount of uncomplexed, monomeric beta-catenin and plakoglobin, detected both by affinity precipitation and size-exclusion chromatography of cell extracts. Exogenous expression of beta-catenin was possible in cells already responding to Wnt-1 but not in the parental cells, suggesting that Wnt-1 inhibits an essential regulatory mechanism for beta-catenin turnover. APC has the capacity to oppose this Wnt-1 effect in experiments in which overexpression of the central region of APC significantly reduced the size of the monomeric pool of beta-catenin induced by Wnt-1. Thus, the Wnt-1 signal transduction pathway leads to the accumulation of monomeric catenins and stabilization of catenin complex formation with both APC and cadherins.
机译：Wnt-1原癌基因诱导β-catenin和plakoglobin的积累，这是两个与钙粘蛋白粘附蛋白相关并在功能上调节它们的相关蛋白。在这里，我们研究了Wnt-1表达对抑癌蛋白APC的影响，该蛋白也与连环蛋白相关。 Wnt-1在两种不同细胞系中的表达大大提高了APC-catenin复合物的稳定性。 Wnt-1升高了连环蛋白和APC的稳态水平，并且与APC相关的β-连环蛋白和普拉格珠蛋白的半衰期也显着增加。 Wnt-1对连环蛋白的稳定作用，主要是由于通过细胞沉淀的亲和沉淀和尺寸排阻色谱法检测到的非复合单体β-catenin和plakoglobin选择性增加的结果。 β-catenin的外源表达可能已经在已经响应Wnt-1的细胞中发生了，但在亲代细胞中却没有，这表明Wnt-1抑制了β-catenin周转的重要调控机制。在实验中，APC具有抵抗Wnt-1效应的能力，在实验中，APC中央区域的过表达显着减小了Wnt-1诱导的β-catenin单体库的大小。因此，Wnt-1信号转导途径导致单体连环蛋白的积累和与APC和钙粘着蛋白的连环蛋白复合物形成的稳定。

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