癌症治疗的新靶点——eEF2K  

A novel target for cancer therapy——eEF2K

作　　者：肖婷[1] 刘锐[1] 王明伟[1] 

机构地区：[1]中国科学院上海药物研究所国家新药筛选中心,上海201203

出　　处：《生命的化学》2016年第3期397-403,共7页Chemistry of Life

基　　金：国家科技重大专项(2012ZX09304-011;2013ZX09401003-005;2013ZX09507001;2013ZX09507-002);上海市科学技术委员会基金项目(13DZ2290300;15DZ2291600)

摘　　要：真核生物延伸因子2激酶(eukaryotic elongation factor 2 kinase,eEF2K)由人类基因组eEF2K基因编码,归属于"α-激酶"非典型蛋白激酶小家族。eEF2K的活性要依赖于钙离子和钙调蛋白。研究显示,eEF2K在一定的代谢压力下能磷酸化并抑制真核生物延伸因子2(eukaryotic elongation factor 2,eEF2),进而抑制蛋白质合成过程中多肽链的延伸,使细胞中能量和氨基酸的消耗减少,帮助细胞适应营养或能量缺乏的不利条件。越来越多的证据显示,eEF2K可成为治疗癌症等疾病药物的新靶点。本文结合近年来报道的eEF2K小分子抑制剂探讨其在癌症等疾病治疗中的潜在价值。Eukaryotic elongation factor 2 kinase（eEF2K） is encoded by the human eEF2K gene. It belongs to an atypical protein kinase family named as ‘α-kinase＇. The activity of eEF2K depends on Ca^（2＋） and calmodulin. Under the condition of certain metabolic stress eEF2K can phosphorylate the eukaryotic elongation factor 2（eEF2） to restrain its activity, to inhibit elongation of polypeptide chains in the process of protein synthesis, and to reduce energy and amino acid consumption, thereby helping cells survive through nutrition deprivation conditions. eEF2K is thus implicated to be a novel drug target for cancer treatment. In conjunction with some newly reported small molecule eEF2K inhibitors, the potential therapeutic value of eEF2K is discussed in this review.

关 键 词：真核生物延伸因子2激酶 多肽链延伸 真核生物延伸因子2激酶抑制剂 高通量药物筛选 

分 类 号：R730.5[医药卫生—肿瘤]