[关键词]
[摘要]
真核细胞翻译起始因子4E(eukaryotic translation initiation factor 4E,eIF4E)是与恶性肿瘤密切相关的因子之一,可与mRNA的5′端帽子结构特异性结合,在蛋白质合成的起始阶段发挥重要的调控作用。eIF4E的活性受自身磷酸化、翻译抑制蛋白的磷酸化及核内因子等因素的调节。eIF4E高表达于多种人类恶性肿瘤中,与肿瘤的发生、浸润和转移密切相关。目前已有一些以eIF4E为肿瘤治疗靶点的研究,如小分子干扰RNAs抑制eIF4E的表达、药物阻断AKT/mTOR或Raf/MEK/ERK信号通路、小分子抑制剂4EG1抑制帽依赖性翻译等,它们通过阻断eIF4E磷酸化抑制肿瘤细胞生长。总之,eIF4E有望成为恶性肿瘤生物治疗的新靶点。
[Key word]
[Abstract]
Eukaryotic translation initiation factor 4E (eIF4E) is one of the factors closely associated with the malignant tumors. It can specifically bind to the cap structure of mRNA 5′end and plays an important role in regulating the initial stage of protein synthesis. The activity of eIF4E is regulated by the phosphorylation, the phosphorylation of translation inhibitory protein and nuclear factors. EIF4E is highly expressed in many human malignancies and is related to development, invasion and metastasis of tumors. Previous researches about eIF4E have indicated it as a cancer therapeutic target; these researches included those using small interfering RNAs to suppress the expression of eIF4E, drugs to block AKT/mTOR or Raf/MEK/ERK signaling pathways, small molecule inhibitor of 4EG1 to inhibit cap-dependent translation; they inhibit tumor growth through decreasing the levels of eIF4E phosphorylation. EIF4E is expected to become a new target for malignant tumor biotherapy.
[中图分类号]
[基金项目]
上海科委重大项目资助(No.05NM05026)