上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (5): 684-689.doi: 10.3969/j.issn.1674-8115.2021.05.021

• 综述 • 上一篇    下一篇

人源核酸烷基化损伤修复酶ALKBH3在肿瘤进展和治疗中的作用

胡静燕(), 张琳, 张良()   

  1. 上海交通大学基础医学院药理学与化学生物学系,上海 200025
  • 出版日期:2021-05-28 发布日期:2021-05-27
  • 通讯作者: 张良 E-mail:hujingyan95@sjtu.edu.cn;liangzhang2014@sjtu.edu.cn
  • 作者简介:胡静燕(1995—),女,硕士生;电子信箱:hujingyan95@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金(21722802);上海交通大学医学院高水平地方高校创新团队(SSMU-ZLCX20180702)

Function of human nucleic acid alkylation damage repair enzyme ALKBH3 in cancer progression and oncotherapy

Jing-yan HU(), Lin ZHANG, Liang ZHANG()   

  1. Department of Pharmacology, Shanghai Jiao Tong University College of Basic Medical Science, Shanghai 200025, China
  • Online:2021-05-28 Published:2021-05-27
  • Contact: Liang ZHANG E-mail:hujingyan95@sjtu.edu.cn;liangzhang2014@sjtu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(21722802);Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZLCX20180702)

摘要:

人源核酸烷基化损伤修复酶ALKBH3(alpha-ketoglutarate-dependent dioxygenase homolog 3)隶属于亚铁(Fe2+)和α-酮戊二酸(α-ketoglutarate,α-KG)依赖型双加氧酶AlkB家族。尽管ALKBH3具有与该家族其他同源蛋白成员高度类似的保守氨基酸序列和三级结构,但是ALKBH3对单链DNA或RNA上的N1-甲基腺嘌呤和N3-甲基胞嘧啶等烷基化损伤具有独特的识别和去除功能。它的表达异常或功能异常与多种癌症的发生发展有紧密联系,被认为是抗肿瘤的潜在药物靶标。对于ALKBH3结构功能和调控机制的深入研究,将有助于进一步了解人体烷基化损伤修复过程中的分子机制,为研发靶向ALKBH3的抗肿瘤药物奠定基础。

关键词: 人源核酸烷基化损伤修复酶, ALKBH3, DNA烷基化损伤修复, 癌症

Abstract:

Human nucleic acid alkylation damage repair enzyme ALKBH3 (alpha-ketoglutarate-dependent dioxygenase homolog 3) belongs to Fe2+/α-Ketoglutarate (α-KG)-dependent AlkB dioxygenase family, and shares a highly conserved catalytic domain through the entire family. ALKBH3 specifically recognizes N1-methyl adenine and N3-methyl cytosine on single-stranded DNA or RNA, and catalyzes their methyl group removal for alkylation damage repair. Previous studies have shown that ALKBH3 is highly expressed in various solid tumors, and thereby it has been considered as a potential anti-tumor drug target. Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNA alkylation damage repair, and lay the foundation for the development of anti-tumor drugs targeting ALKBH3.

Key words: alpha-ketoglutarate-dependent dioxygenase homolog 3, ALKBH3, DNA alkylation damage repair, cancer

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