Tet:基于DNA去甲基化的全新抗肿瘤药物靶标

发布时间：2018-04-16 04:31

  本文选题：DNA去甲基化 + Tet蛋白　； 参考：《上海交通大学学报(医学版)》2017年04期

【摘要】：Tet蛋白属于α-酮戊二酸(α-KG)和亚铁离子(Fe2+)依赖的双加氧酶家族。Tet特异识别基因组DNA上5-甲基胞嘧啶(5mC)的甲基并进行催化氧化,是哺乳动物基因组DNA主动去甲基化途径中唯一被发现的关键因子。通过调控基因组5mC的动态平衡分布,Tet在胚胎发育早期基因调控和胚胎干细胞定向分化中至关重要,其表达和功能异常与包括骨髓增生异常综合征、慢性骨髓单核细胞性白血病和急性白血病在内的多种血液恶性肿瘤以及实体肿瘤有密切关系。因此,Tet及其介导的DNA去甲基化是全新的抗肿瘤靶向药物靶标。对于Tet生物功能和催化机制的研究将有助于深入了解与DNA去甲基化途径相关肿瘤的发生和发展机制,同时也为研发全新的抗肿瘤靶向药物提供参考。
[Abstract]:The Tet protein belongs to 伪 -ketoglutaric acid (伪 -KG) and iron ion (Fe _ 2) -dependent dioxygenase family. Tet specifically recognizes and catalyzes the methylcytosine 5mC- (5-methylcytosine) on genomic DNA.It is the only key factor found in the active demethylation pathway of mammalian genomic DNA.Tet plays an important role in early embryonic development gene regulation and embryonic stem cell differentiation by regulating the dynamic equilibrium distribution of genomic 5mC, and its expression and function are abnormal, including myelodysplastic syndrome (MDS).Chronic myeloid monocytic leukemia and acute leukemia are closely related to various hematologic malignancies and solid tumors.Therefore, Tet and its mediated DNA demethylation are novel targets for anti-tumor drugs.The study on the biological function and catalytic mechanism of Tet will be helpful to understand the mechanism of tumorigenesis and development related to DNA demethylation pathway, and also provide a reference for the development of new anti-tumor targeted drugs.
【作者单位】： 上海交通大学基础医学院药理学教研室;
【基金】：国家自然科学基金(21572133) 上海交通大学医学院“大学生创新训练项目”第十期(2016008)~~
【分类号】：R979.1
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本文编号：1757330