The inner nuclear membrane protein Emerin regulates β-catenin activity by restricting its accumulation in the nucleus
The inner nuclear membrane protein Emerin regulates β-catenin activity by restricting its accumulation in the nucleus
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DOI：
10.1038/sj.emboj.7601230
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发表时间：
2006-07-26
期刊：
影响因子：
11.4
通讯作者：
Hutchison, Christopher J.
中科院分区：
文献类型：
--
作者：
Markiewicz, Ewa;Tilgner, Katarzyna;Hutchison, Christopher J.
Emerin是一种功能未知的II型内核膜蛋白。Emerin功能可能很重要，因为当Emerin发生突变时，它会同时促进骨骼肌和心脏缺陷。在这里，我们证明了Emerin的一个功能是调节β-连环蛋白的流量，β-连环蛋白是一种重要的转录共激活因子，进入细胞核。Emerin通过保守的腺瘤性息肉病结肠(APC)样结构域与β-连环蛋白相互作用。当GFP-Emerin在HEK293细胞中表达时，β-catenin被限制在细胞质中，并且β-catenin的活性被抑制。相反，缺乏APC样结构域(GFP-Emerin Delta)的Emerin突变体的表达主要刺激β-catenin活性并增加β-catenin的核积累。Emerin基因缺失的人成纤维细胞具有自我刺激生长表型。这种不寻常的生长表型是通过增强β-连环蛋白的核积累和活性而产生的，并可以通过转染具有结构性活性的β-连环蛋白在野生型成纤维细胞中复制。我们的结果支持了最近的发现，即INM蛋白可以通过限制转录共激活子进入细胞核来影响信号通路。
Emerin is a type II inner nuclear membrane (INM) protein of unknown function. Emerin function is likely to be important because, when it is mutated, emerin promotes both skeletal muscle and heart defects. Here we show that one function of Emerin is to regulate the flux of beta-catenin, an important transcription coactivator, into the nucleus. Emerin interacts with beta-catenin through a conserved adenomatous polyposis coli (APC)-like domain. When GFP-emerin is expressed in HEK293 cells, beta-catenin is restricted to the cytoplasm and beta-catenin activity is inhibited. In contrast, expression of an emerin mutant, lacking its APC-like domain (GFP-emerin Delta), dominantly stimulates beta-catenin activity and increases nuclear accumulation of beta-catenin. Human fibroblasts that are null for emerin have an autostimulatory growth phenotype. This unusual growth phenotype arises through enhanced nuclear accumulation and activity of beta-catenin and can be replicated in wild-type fibroblasts by transfection with constitutively active beta-catenin. Our results support recent findings that suggest that INM proteins can influence signalling pathways by restricting access of transcription coactivators to the nucleus.