本文選題：DNA去甲基化 + Tet蛋白　； 參考：《上海交通大學學報(醫(yī)學版)》2017年04期

【摘要】：Tet蛋白屬于α-酮戊二酸(α-KG)和亞鐵離子(Fe2+)依賴的雙加氧酶家族。Tet特異識別基因組DNA上5-甲基胞嘧啶(5mC)的甲基并進行催化氧化,是哺乳動物基因組DNA主動去甲基化途徑中唯一被發(fā)現(xiàn)的關鍵因子。通過調(diào)控基因組5mC的動態(tài)平衡分布,Tet在胚胎發(fā)育早期基因調(diào)控和胚胎干細胞定向分化中至關重要,其表達和功能異常與包括骨髓增生異常綜合征、慢性骨髓單核細胞性白血病和急性白血病在內(nèi)的多種血液惡性腫瘤以及實體腫瘤有密切關系。因此,Tet及其介導的DNA去甲基化是全新的抗腫瘤靶向藥物靶標。對于Tet生物功能和催化機制的研究將有助于深入了解與DNA去甲基化途徑相關腫瘤的發(fā)生和發(fā)展機制,同時也為研發(fā)全新的抗腫瘤靶向藥物提供參考。
[Abstract]:The Tet protein belongs to 偽 -ketoglutaric acid (偽 -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.
【作者單位】： 上海交通大學基礎醫(yī)學院藥理學教研室;
【基金】：國家自然科學基金(21572133) 上海交通大學醫(yī)學院“大學生創(chuàng)新訓練項目”第十期(2016008)~~
【分類號】：R979.1
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本文編號：1757330