真核起始因子5A与细胞周期G_1-S调控的研究  

The Effect of eIF-5A on the G_1-S in Cell Cycle Regulation

作　　者：靳宝锋[1] 何昆[2] 胡美茹[1] 于鸣[1] 沈倍奋[1] 张学敏[2] 

机构地区：[1]军事医学科学院基础医学研究所免疫室,北京100850 [2]国家生物医学分析中心,北京100850

出　　处：《中国实验血液学杂志》2003年第4期325-328,共4页Journal of Experimental Hematology

基　　金：国家高技术研究发展计划"863"资助项目 编号2 0 0 1AA2 3 3 0 41

摘　　要：真核启始因子 5A(eIF 5A)翻译后第 4 9位的赖氨酸被修饰为一个特殊氨基酸hypusine ,后者是其发挥功能所必需的。本研究用eIF 5A翻译后hypusine修饰的特异性阻断剂 1,7 二氨基庚烷 (1,7 diaminoheptane ,DAH)处理白血病细胞系 (TF 1,THP 1和Mo7e)和人乳腺癌细胞系 (MCF 7) ,用FCM和台盼蓝拒染法检测其对细胞增殖和活性的影响 ;应用两步胸腺嘧啶核苷阻断法使细胞周期同步化 ,并用免疫印迹法检测eIF 5A在细胞周期时相的表达情况。结果表明 :用 1,7 二氨基庚烷处理后 ,细胞生长明显受到抑制 ,并有一定的促凋亡效应 ;且细胞周期被特异性阻滞于G1/S期 ;eIF 5A在细胞周期的S期和G2 /M期的表达量较低 ,在G1期表达量明显增加。结论 :eIF 5A的hypusine修饰参与了细胞周期调控 。Eukaryotic initiation factor 5A (eIF 5A) contains an unusual amino acid, hypusine, which is formed post translationally. Although eIF 5A and its hypusine modification are essential for eukaryotic cell viability, the precise physiological function of it has remained elusive. The aim of the study is to investigate how hypusine formation modulate the proliferation, cell cycle and apoptosis in leukaemia cells. The effects of 1,7 diaminoheptane (DAH), a potent inhibitor of deoxyhypusine synthase, on proliferation and cell viability of leukemia cell lines (Mo7e, TF 1 and THP 1) and MCF 7 cells, were investigated. eIF 5A expression level was detected after cell synchronization. The results showed that inhibition of cell proliferation by DAH was in a concentration dependent manner while apoptosis was also induced at the same time. Upon treatment of the cell lines with DAH, cell growth was inhibited. Cell cycle analysis showed that DAH induced cell growth arrest at the G 1 S boundary of the cell cycle. In synchronized MCF 7 cells, the expression level of eIF 5A peaked at G 1 phase but very low at S and G 2/M phases. It is concluded that hypusine formation of eIF 5A exits in the regulation of cell cycle and the results suggest that eIF 5A is involved in the expression of proteins regulating transition of G 1 S phase of cell cycle.

关 键 词：真核起始因子5A HYPUSINE 细胞同步化 细胞周期调控 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]