TET2在血液系统疾病中的作用

Role of TET2 in hematopoietic diseases

TET(ten-eleven translocation)家族蛋白是生物体内存在的一种α-酮戊二酸(α-KG)和Fe2+依赖的双加氧酶,TET蛋白可以催化5-甲基胞嘧啶(5-methyl-cytosine,5m C)转化为(5-hydroxymethyl-cytosine,5hm C),是DNA去甲基化过程中的一种重要的酶,对于维持干细胞的多能性有重要作用。人TET蛋白家族有三个成员,分别为TET1、TET2和TET3。TET1最早被鉴定有催化5-m C羟基化的酶活性,进一步研究发现,三种TET蛋白均具有将5-m C转化为5-hm C的能力。TET2是进化上高度保守的TET家族成员之一,大多数动物都有一个单一的TET同源基因,其编码产物的特征为氨基酸末端CXXC锌指结构域和羧基端α-酮戊二酸(α-KG)和Fe^(2+)依赖的双加氧酶催化结构域以及一个富含半胱氨酸的区域。近年在多种血液系统肿瘤中发现存在TET2突变,提示TET2在血液系统中存在重要作用,敲除小鼠模型实验也证实了这一点。本文将对TET2的结构、功能以及其与血液系统疾病的关系进行综述。

TET（ten-eleven translocation） dioxygenases require a-KG and Fe（II） for their activity. They catalyze the conversion of 5-mC to 5-hmC, and play important roles in DNA methylation and pluripotency of stem cells. TET family of proteins are comprised of three family members, TET1, TET2 and TET3. TET1 was first found. Subsequent searches have identified two additional members,TET2 and TET3. TET2 is the evolutionarily highly conserved protein and most animals have only one single homologous gene ofTET. TET protein typically possess a CXXC domain at the amino-terminal region and a catalytic domain consistiong of a cysteine-rich and a double-stranded [^-helix dioxygenase domain at the carboxy-terminal region. Recent studies revealed TET2 inactivation is a common event in a variety of human hematological malignancies, sug- gesting a critical role for TET2 in hematopoiesis. The Tet2 mutation mouse models also proved the point. The review summarizes the structure and function of TET2 and focuses on its role in hematopoiesis.