真核翻译起始因子eIF3A导致的翻译起始异常和相关疾病(英文)  

Aberration in translation initiation and associated diseases:Role of the eukaryotic translation initiation factor 3A

作　　者：朱涛 高元峰 李玲[1,2] 王蕾云[1,2] 尹继业 周宏灏[1,2] 张伟[1,2] 刘昭前[1,2] 

机构地区：[1]中南大学湘雅医院临床药理研究所,长沙410008 [2]中南大学临床药理研究所,湖南省遗传药理学重点实验室,长沙410078

出　　处：《中南大学学报（医学版）》2017年第10期1204-1211,共8页Journal of Central South University ：Medical Science

基　　金：supported by the National Key Research and Development Plan(SQ2016YFSF110100,2016YFC0905000);National Natural Science Foundation(81373490,81573508,81573463);Hunan Provincial Science and Technology Plan(2015JC3025);Open Foundation of Innovative Platform in University of Hunan Province(421530004),China

摘　　要：真核生物翻译控制在细胞进程中对基因表达调控具有重要作用,能确保蛋白的迅速调节以维持细胞内稳态。真核翻译是一个多步骤的过程,包括起始、延伸、终止和核糖体循环,其中起始是限速步骤,受真核翻译起始因子(eukaryotic translation initiation factors,eIFs)调控。翻译起始缺陷将导致一系列疾病。在所有eIFs中,eIF3是最大的同时知之较少的因子。eIF3A是eIF3因子的最大亚基,其异常一方面会导致肿瘤发生,另一方面将阻止肿瘤向更高级别恶性肿瘤进展。eIF3A表达变化和突变影响肿瘤患者对铂类化疗药物的反应。此外,eIF3A与纤维化病变相关,抑制eIF3A的试剂能延缓病变进展。eIF3A在肿瘤中的双重作用可能是其在肿瘤进展的不同阶段调节不同mRNAs翻译的结果,特定阶段不同mRNAs的编码产物发挥促癌或抑癌作用。Translation control in eukaryotes contributes significantly to gene expression regulation during cellular processes, which enables rapid changes of specific proteins to maintain cellular homeostasis. Eukaryotic translation is a multiple-step process that comprised of four phases： initiation, elongation, termination and ribosome recycling. The initiation phase is rate-limiting and orchestrated by a set of eukaryotic translation initiation factors （elFs）. Defects in translation initiation can result in a series of diseases. Among all elFs, eIF3 is the largest and less-known initiation factor due to its intrinsic complexity. Aberration in elF3A, the largest subunit of elF3, is known to contribute to carcinogenesis and protection against evolution into higher-grade malignancy; and the altered expression or mutation of elF3A affects the responses of cancer patients to platinum-based chemotherapy. Besides its role in cancinogenesis, eIF3A is also implicated in fibrosis, and the agents inhibiting elF3A delay the progression of this disorder. Xhe dual roles of elF3A in tumorigenesis are probably due to the regulation of translation of different mRNAs at different stages of tumor progression by eIF3A. In turn the encoded products serve as pro-tumor or anti-tumor proteins at different stages.

关 键 词：翻译起始 真核翻译起始因子3A 癌症 纤维化 铂类药物化疗 

分 类 号：R363[医药卫生—病理学]