Center for Inflammation Research, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Biosci Rep. 2019 Aug 2;39(8). doi: 10.1042/BSR20180604. Print 2019 Aug 30.
Armadillo-repeat-containing protein 8 (Armc8) belongs to the family of armadillo-repeat containing proteins, which have been found to be involved in diverse cellular functions including cell-cell contacts and intracellular signaling. By comparative analyses of armadillo repeat protein structures and genomes from various premetazoan and metazoan species, we identified orthologs of human Armc8 and analyzed in detail the evolutionary relationship of genes and their encoded proteins. Armc8 is a highly ancestral armadillo protein although not present in yeast. Consequently, Armc8 is not the human ortholog of yeast Gid5/Vid28.Further, we performed a candidate approach to characterize new protein interactors of Armc8. Interactions between Armc8 and specific δ-catenins (plakophilins-1, -2, -3 and p0071) were observed by the yeast two-hybrid approach and confirmed by co-immunoprecipitation and co-localization. We also showed that Armc8 interacts specifically with αE-catenin but neither with αN-catenin nor with αT-catenin. Degradation of αE-catenin has been reported to be important in cancer and to be regulated by Armc8. A similar process may occur with respect to plakophilins in desmosomes. Deregulation of desmosomal proteins has been considered to contribute to tumorigenesis.
棘皮动物重复蛋白 8（Armc8）属于棘皮动物重复蛋白家族，该家族蛋白参与多种细胞功能，包括细胞-细胞接触和细胞内信号转导。通过对各种前原生动物和后生动物的棘皮动物重复蛋白结构和基因组的比较分析，我们鉴定了人类 Armc8 的同源物，并详细分析了基因及其编码蛋白的进化关系。Armc8 是一种高度保守的棘皮动物蛋白，尽管在酵母中不存在。因此，Armc8 不是酵母 Gid5/Vid28 的人类同源物。此外，我们采用候选方法来鉴定 Armc8 的新蛋白相互作用物。通过酵母双杂交实验观察到 Armc8 与特定的 δ-连环蛋白（ plakophilin-1、-2、-3 和 p0071）之间的相互作用，并通过共免疫沉淀和共定位实验进行了验证。我们还表明，Armc8 与 αE-连环蛋白特异性相互作用，但与 αN-连环蛋白或 αT-连环蛋白均不相互作用。αE-连环蛋白的降解已被报道在癌症中很重要，并受 Armc8 调节。在桥粒中，类似的过程可能发生在 plakophilin 上。桥粒蛋白的失调被认为有助于肿瘤发生。
