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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Thymidylate synthase as a translational regulator of cellular gene expression
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Thymidylate synthase as a translational regulator of cellular gene expression

机译：胸苷酸合酶作为细胞基因表达的翻译调控因子

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摘要

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 poteins. 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.
机译：我们实验室的研究表明，叶酸依赖性酶胸苷酸合酶（TS）可作为RNA结合蛋白。有证据表明，TS除了与其自身的TS mRNA相互作用外，还与许多其他细胞mRNA形成核糖核蛋白复合物，包括与p53抑癌基因和myc转录因子家族相对应的mRNA。使用体外和体内模型系统，我们已经证明，TS蛋白与其自身同源mRNA结合以及TS与p53 mRNA结合的功能后果是翻译抑制。在本文中，我们回顾了目前对TS表达的翻译自动调节控制的工作，并讨论了TS蛋白-TS mRNA相互作用所需的分子元件。 TS通过调节p53和其他可能与细胞周期相关的蛋白表达，可能在调节细胞周期和凋亡过程中起关键作用。最后，就细胞对各种抗癌药物的耐药性发展而言，TS发挥翻译调节剂的功能可能会产生重要的后果。

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