Thymidylate synthase as a translational regulator of cellular gene expression
Thymidylate synthase as a translational regulator of cellular gene expression
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DOI：
10.1016/s0925-4439(02)00080-7
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发表时间：
2002-07-18
影响因子：
6.2
通讯作者：
Chu, E
中科院分区：
文献类型：
--
作者：
Liu, J;Schmitz, JC;Chu, E
我们实验室的研究表明，叶酸依赖性酶胸苷酸合成酶（TS）作为RNA结合蛋白发挥作用。有证据表明，TS，除了与自己的TS mRNA相互作用，形成一个核糖核蛋白复合物与其他细胞的mRNA，包括那些相应的p53肿瘤抑制基因和myc家族的转录因子。使用在体外和体内模型系统，我们已经证明，TS蛋白结合到它自己的同源mRNA的功能性后果，以及TS的p53 mRNA的结合，是翻译抑制。在此，我们回顾了目前的工作，TS表达的翻译自动调节控制和讨论的TS蛋白TS mRNA相互作用所需的分子元件。TS可能通过调节p53和其他细胞周期相关蛋白的表达，在调节细胞周期和凋亡过程中发挥关键作用。最后，TS作为翻译调节剂的功能可能对细胞对各种抗癌药物的耐药性的发展产生重要影响。(C)2002 Elsevier Science B.V保留所有权利。
Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein. There is evidence that TS, in addition to interacting with its own TS mRNA, forms a ribonucleoprotein complex with a number of other cellular mRNAs, including those corresponding to the p53 tumor suppressor gene and the myc family of transcription factors. Using both in vitro and in vivo model systems, we have demonstrated that the functional consequence of binding of TS protein to its own cognate mRNA, as well as binding of TS to the p53 mRNA, is translational repression. Herein, we review current work on the translational autoregulatory control of TS expression and discuss the molecular elements that are required for the TS protein-TS mRNA interaction. TS may play a critical role in regulating the cell cycle and the process of apoptosis through its regulatory effects on expression of p53 and perhaps other cell cycle related proteins. Finally, the ability of TS to function as a translational regulator may have important consequences with regard to the development of cellular resistance to various anticancer drugs. (C) 2002 Elsevier Science B.V All rights reserved.