Shrestha Hridaya, Ryu Taeyong, Seo Young-Woo, Park So-Yeon, He Yongfeng, Dai Weiye, Park Eunsook, Simkhada Shishli, Kim Hangun, Lee Keesook, Kim Kwonseop
College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
Korea Basic Science Institute, Gwangju Center at Chonnam National University, Gwangju, South Korea.
Cell Signal. 2017 Feb;31:135-145. doi: 10.1016/j.cellsig.2017.01.009. Epub 2017 Jan 6.
Hakai ubiquitinates and induces endocytosis of the E-cadherin complex; thus, modulating cell adhesion and regulating development of the epithelial-mesenchymal transition of metastasis. Our previous published data show that δ-catenin promotes E-cadherin processing and thereby activates β-catenin-mediated oncogenic signals. Although several published data show the interactions between δ-catenin and E-cadherin and between Hakai and E-cadherin separately, we found no published report on the relationship between δ-catenin and Hakai. In this report, we show Hakai stabilizes δ-catenin regardless of its E3 ligase activity. We show that Hakai and Src increase the stability of δ-catenin synergistically. Hakai stabilizes Src and Src, which in turn, inhibits binding between glycogen synthase kinase-3β and δ-catenin, resulting in less proteosomal degradation of δ-catenin. These results suggest that stabilization of δ-catenin by Hakai is dependent on Src.
Hakai使E-钙黏蛋白复合体发生泛素化并诱导其胞吞作用;因此,调节细胞黏附并调控转移过程中上皮-间质转化的发展。我们之前发表的数据表明,δ-连环蛋白促进E-钙黏蛋白的加工处理,从而激活β-连环蛋白介导的致癌信号。尽管有几篇已发表的数据分别显示了δ-连环蛋白与E-钙黏蛋白之间以及Hakai与E-钙黏蛋白之间的相互作用,但我们未发现有关δ-连环蛋白与Hakai之间关系的已发表报告。在本报告中,我们表明,无论Hakai的E3连接酶活性如何,它都能使δ-连环蛋白稳定。我们发现,Hakai和Src协同增加δ-连环蛋白的稳定性。Hakai使Src稳定,而Src反过来抑制糖原合酶激酶-3β与δ-连环蛋白之间的结合,导致δ-连环蛋白的蛋白酶体降解减少。这些结果表明,Hakai对δ-连环蛋白的稳定作用依赖于Src。