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论文摘要

1011易位甲基胞嘧啶双加氧酶-1的结构和去甲基化作用及生物学功能

Structure, demethylation activity, and biological function of 1011 translocation methylcytosine dioxygenase-1

作者:饶利佳 李启梦 徐琼

Author:Rao Lijia, Li Qimeng, Xu Qiong

收稿日期:2014-09-28          年卷(期)页码:2015,42(3):323-327

期刊名称:国际口腔医学杂志

Journal Name:International Journal of Stomatology

关键字:1011易位甲基胞嘧啶双加氧酶,DNA甲基化,DNA去甲基化,5-甲基胞嘧啶,5-羟甲基胞嘧啶,

Key words:ten-eleven translocation methylcytosine dioxygenase,DNA methylation,DNA demethylation,5-methyl cytosine,5-hydroxymethyl cytosine,

基金项目:

中文摘要

1011易位甲基胞嘧啶双加氧酶(TET)-1是发挥DNA去甲基化作用重要的蛋白质之一,始见于急性髓系白血病相关的染色体易位t(10;11)(q22;q23)的白血病患者,其C端为双加氧酶区,是TET-1的主要催化功能结构域,可将5-甲基胞嘧啶(5-mC)氧化为5-羟甲基胞嘧啶,经主动或被动去甲基化实现DNA去甲基化。TET-1通过参与DNA去甲基化调节基因表达,在胚胎发育、体细胞重编程、肿瘤发生、神经细胞发生发育等过程发挥作用,在成体细胞中参与调控细胞分化与增殖。TET-1蛋白及其介导的5-mC羟甲基化过程深化了人们对DNA碱基修饰多样性及复杂性的认识,其在干细胞增殖与分化和肿瘤发生等过程中的功能研究,为诸多生理现象和疾病发生发展作了新的诠释。

英文摘要

Ten-eleven translocation methyl cytosine dioxygenase(TET)-1, one of the important protein in DNA demethylation pathway, is found in acute myeloid leukemia and is associated with chromosomal translocation t(10;11) (q22;q23) in patients with leukemia. The C-terminal dioxygenase district is the main catalytic functional domain of TET-1, can oxidized five methylcytosine(5-mC) into 5-hydroxymethyl cytosine. TET-1 plays a role in embryogenesis, somatic cell reprogramming, tumorigenesis, development of nerve cells, and regulation of cell differentiation and proliferation in adult cells by participating in demethylation and regulation of DNA gene expression. The hydroxy methylation of 5-mC in the TET-1 protein has elucidated the diversity and complexity of DNA gene expression. This mechanism has also been used in stem cell proliferation, differentiation, and tumorigenesis for functional studies of many physiological phenomena to provide novel interpretation for the occurrence and development of diseases.

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