Hatzfeld Mechthild, Wolf Annika, Keil René
Division of Pathobiochemistry, Institute of Molecular Medicine, Martin-Luther-University Halle-Wittenberg , Halle , Germany.
Cell Commun Adhes. 2014 Feb;21(1):25-42. doi: 10.3109/15419061.2013.876017.
The regulation of adhesion and growth is important for epithelial function and dysfunction. β-catenin (armadillo in Drosophila) is the prototype of a multifunctional molecule that regulates cell adhesion via adherens junctions and cell signaling via LEF/TCF transcription factors. Desmosomal armadillo proteins comprise plakoglobin and the plakophilins 1, 2, and 3. These proteins are essential for building up the desmosome and linking the desmosomal cadherins to keratin filaments. High expression of plakophilins in desmosomes correlates with strong intercellular cohesion and is essential for tissue integrity under mechanical stress. However, like β-catenin, these proteins have diverse non-desmosomal functions, for example, in regulating actin organization, protein synthesis, and growth control. In line with these functions, their de-regulated expression with up- as well as down-regulation has been connected to cancer and metastasis. Now, recent evidence sheds light on the post-translational regulation and provides an explanation for how de-regulation of plakophilins can contribute to cancer.
黏附与生长的调节对于上皮功能及功能障碍至关重要。β-连环蛋白（果蝇中的犰狳蛋白）是一种多功能分子的原型，它通过黏附连接调节细胞黏附，并通过LEF/TCF转录因子调节细胞信号传导。桥粒犰狳蛋白包括桥粒斑珠蛋白以及桥粒斑菲素蛋白1、2和3。这些蛋白质对于构建桥粒以及将桥粒钙黏蛋白与角蛋白丝连接至关重要。桥粒斑菲素蛋白在桥粒中的高表达与强大的细胞间黏附相关，并且对于机械应力下的组织完整性至关重要。然而，与β-连环蛋白一样，这些蛋白质具有多种非桥粒功能，例如，在调节肌动蛋白组织、蛋白质合成和生长控制方面。与这些功能一致，它们表达失调，包括上调和下调，都与癌症和转移有关。现在，最近的证据揭示了翻译后调节，并解释了桥粒斑菲素蛋白的失调如何导致癌症。
