Division of Pathobiochemistry, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany.
J Cell Biol. 2010 Feb 22;188(4):463-71. doi: 10.1083/jcb.200908135. Epub 2010 Feb 15.
Plakophilins 1-3 (PKP1-3) are desmosomal proteins of the p120(ctn) family of armadillo-related proteins that are essential for organizing the desmosomal plaque. Recent findings identified PKPs in stress granules, suggesting an association with the translational machinery. However, a role of PKPs in controlling translation remained elusive so far. In this study, we show a direct association of PKP1 with the eukaryotic translation initiation factor 4A1 (eIF4A1). PKP1 stimulated eIF4A1-dependent translation via messenger RNA cap and encephalomyocarditis virus internal ribosomal entry site (IRES) structures, whereas eIF4A1-independent translation via hepatitis C virus IRES was not affected. PKP1 copurified with eIF4A1 in the cap complex, and its overexpression stimulated eIF4A1 recruitment into cap-binding complexes. At the molecular level, PKP1 directly promoted eIF4A1 adenosine triphosphatase activity. The stimulation of translation upon PKP1 overexpression correlated with the up-regulation of proliferation and cell size. In conclusion, these findings identify PKP1 as a regulator of translation and proliferation via modulation of eIF4A1 activity and suggest that PKP1 controls cell growth in physiological and pathological conditions.
plakophilins 1-3 (PKP1-3) 是桥粒斑蛋白，属于桥粒斑相关蛋白 p120(ctn) 家族的锚蛋白重复蛋白，对于桥粒斑的组织化至关重要。最近的研究结果发现 PKPs 存在于应激颗粒中，这表明它们与翻译机制有关。然而，PKPs 控制翻译的作用目前仍不清楚。在这项研究中，我们发现 PKP1 与真核翻译起始因子 4A1 (eIF4A1) 有直接的关联。PKP1 通过信使 RNA 帽和脑心肌炎病毒内部核糖体进入位点 (IRES) 结构刺激 eIF4A1 依赖性翻译，而不影响通过丙型肝炎病毒 IRES 的 eIF4A1 非依赖性翻译。PKP1 在帽复合物中与 eIF4A1 共纯化，其过表达刺激 eIF4A1 招募到帽结合复合物中。在分子水平上，PKP1 直接促进 eIF4A1 的三磷酸腺苷酶活性。PKP1 过表达引起的翻译刺激与增殖和细胞大小的上调相关。总之，这些发现表明 PKP1 通过调节 eIF4A1 的活性来控制翻译和增殖，并表明 PKP1 在生理和病理条件下控制细胞生长。
