翻译起始因子与肿瘤翻译调控异常研究进展

蛋白合成是维持细胞稳态和细胞增殖的关键步骤。翻译过程的调控多发生在蛋白合成起始过程,多种翻译起始因子(eIFs)参与此过程。在细胞恶性表型转化过程中,常伴随这些因子的磷酸化、过表达及降解过程异常。如帽结合蛋白eIF4E高表达,甲硫氨酸-tRNA结合蛋白eIF2过度活跃,eIF3的活性增高等现象。eIFs在蛋白合成及细胞增殖过程中的重要地位使得其成为抗肿瘤研究的热点及潜在的治疗靶点。本文对eIFs及肿瘤翻译调控的研究进展及研究方法进行综述。

Translation initiation factors and abnormalities of translation control in tumors

Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Most translational controls occur during the initiation phase of protein synthesis recruiting several translation initiation factors (eIFs), with the initiation factors being the major target of regulation through their phosphorylation. When the process of protein synthesis is hyper-activated, abnormalities in the phosphorylation, expression and degradation were frequently observed, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overexpressed, or when the methionyl-tRNAi-binding factor, eIF2, is too active, and when eIF3 hyper-activated. The importance of eIFs as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer. This review focuses on eIFs and mechanisms of translational control and how disregulation results in cell malignancy.