胸苷酸合成酶表达调控的分子机制  

Molecular Mechanisms Regulating the Expression of Thymidylate Synthase

作　　者：阎松[1] 牛荣丽[1] CHU Edward 林秀坤[1] 

机构地区：[1]中国科学院海洋研究所实验海洋生物学重点实验室 [2]耶鲁大学医学院医学与药理学系,newhavenct06520

出　　处：《细胞生物学杂志》2005年第2期105-108,共4页Chinese Journal of Cell Biology

基　　金：国家自然科学基金资助项目(No.30472043)~~

摘　　要：胸苷酸合成酶(thymidylate synthase,TS)是生物体内催化胸苷酸合成所必需的酶,多年来一直作为肿瘤化疗的重要靶酶。对TS基因调控机制的研究表明:基因扩增、转录、翻译和翻译后过程都参与了TS表达的调控。先前的研究表明:TS可与自身的mRNA结合形成TS-mRNA复合物,使mRNA翻译受阻,5-氟尿嘧啶(5-fluorouracil,5-FU)等抗代谢药物可与TS蛋白结合,结合后的复合物不能与TS mRNA作用,导致体内TS的表达升高,是肿瘤细胞产生抗药性的重要分子机制之一。现对TS基因表达调控研究进展、翻译调控与抗药性产生的分子机制进行综述。Thymidylate synthase (TS), an essential enzyme for catalyzing the biosynthesis of thymidylate, is a critical therapeutic target in cancer therapy. Previous study indicated that the level of gene amplification, transcription, translation, and posttranslation were all involved in regulating the expression of TS. Studies have shown that TS was able to bind to its own mRNA to form TS protein-TS mRNA complex, and this interaction resulted in translational suppression. When TS is bound by 5-fluorouracil (5-FU) or other antimetabolite, the RNA binding activity of TS is dramatically decreased. The effect of reduced RNA binding activity is relief of translational repression, a process that leads to increased synthesis of new TS protein. Thus, this model provides a rational mechanism for the devel- opment of drug resistance in tumor cells. In this paper, the mechanisms regulating the expression of TS gene were reviewed, and the ability of TS to function as a translational regulator and the molecular mechanisms of drug resistance were also presented.

关 键 词：胸苷酸合成酶 分子机制 基因调控 抗药性 抗肿瘤药物 

分 类 号：Q785[生物学—分子生物学]