Wang Xuemin, Xie Jianling, Proud Christopher G.
South Australian Health & Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia;
Department of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
Cancers (Basel). 2017 Nov 27;9(12):162. doi: 10.3390/cancers9120162.
Eukaryotic elongation factor 2 kinase (eEF2K) is a highly unusual protein kinase that negatively regulates the elongation step of protein synthesis. This step uses the vast majority of the large amount of energy and amino acids required for protein synthesis. eEF2K activity is controlled by an array of regulatory inputs, including inhibition by signalling through mammalian target of rapamycin complex 1 (mTORC1). eEF2K is activated under conditions of stress, such as energy depletion or nutrient deprivation, which can arise in poorly-vascularised tumours. In many such stress conditions, eEF2K exerts cytoprotective effects. A growing body of data indicates eEF2K aids the growth of solid tumours in vivo. Since eEF2K is not essential (in mice) under 'normal' conditions, eEF2K may be a useful target in the treatment of solid tumours. However, some reports suggest that eEF2K may actually impair tumorigenesis in some situations. Such a dual role of eEF2K in cancer would be analogous to the situation for other pathways involved in cell metabolism, such as autophagy and mTORC1. Further studies are needed to define the role of eEF2K in different tumour types and at differing stages in tumorigenesis, and to assess its utility as a therapeutic target in oncology.
真核生物延伸因子2激酶(eEF2K)是一种极为特殊的蛋白激酶,它对蛋白质合成的延伸步骤起负调控作用。这一步骤消耗了蛋白质合成所需的大量能量和氨基酸中的绝大部分。eEF2K的活性受一系列调控输入的控制,包括通过雷帕霉素靶蛋白复合物1(mTORC1)信号传导产生的抑制作用。在诸如能量耗竭或营养剥夺等应激条件下,eEF2K会被激活,而这些情况可能出现在血管化不良的肿瘤中。在许多此类应激条件下,eEF2K发挥细胞保护作用。越来越多的数据表明,eEF2K在体内有助于实体瘤的生长。由于在“正常”条件下(在小鼠中)eEF2K并非必需,因此eEF2K可能是治疗实体瘤的一个有用靶点。然而,一些报告表明,在某些情况下,eEF2K实际上可能会损害肿瘤发生。eEF2K在癌症中的这种双重作用与细胞代谢中涉及的其他途径(如自噬和mTORC1)的情况类似。需要进一步研究来确定eEF2K在不同肿瘤类型和肿瘤发生的不同阶段所起的作用,并评估其作为肿瘤治疗靶点的效用。