生物学杂志

生物学杂志 ›› 2020, Vol. 37 ›› Issue (5): 90-.doi: 10.3969/j.issn.2095-1736.2020.05.090

• 综述与专论 • 上一篇    下一篇

泛素连接酶UBE4B的研究进展

  

  1. 上海交通大学 药学院， 上海 200240
  • 出版日期:2020-10-18 发布日期:2020-10-14
  • 通讯作者: 武正华，副研究员，硕士生导师，研究方向为蛋白质与多肽的降解及调控、抗肿瘤靶标发现和新型生物技术药物研发，E-mail：wuzhenghua@sjtu.edu.cn
  • 作者简介:陆瑶，硕士研究生，研究方向为蛋白质与多肽的降解及调控，E-mail：luyao28@sjtu.edu.cn

The progress on the ubiquitin ligase UBE4B

  1. School of Pharmacy， Shanghai Jiao Tong University， Shanghai 200240， China
  • Online:2020-10-18 Published:2020-10-14

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摘要： 泛素化是一类重要的蛋白质翻译后修饰，参与了体内多种生命活动。UBE4B作为泛素连接酶U-box家族的一员，含有一种约70个氨基酸组成的特征性U-box结构域，负责底物识别和结合。UBE4B还具有一种特殊的E4活性，可以在E1、E2和E3存在的情况下继续对泛素链进行延长。UBE4B参与了胚胎发育、神经元保护等一系列重要生命过程，它还可降解多种具有重要生理功能的底物，如p53、EGFR、FEZ1及Ataxin-3等，与癌症、神经退行性疾病、肥胖等疾病的发生发展有关。因此研究UBE4B参与的底物调控对于疾病治疗和新药开发有重大意义。从UBE4B的结构特征、生理功能、相关疾病与底物功能等方面，对近20年的研究进展进行了综述及展望，为后续深入研究UBE4B对生命活动的影响提供理论基础。

关键词: 泛素化, 泛素连接酶, UBE4B, U-box, E4

Abstract: Ubiquitination is an important post-translational modification (PTMs), regulating several cellular functions. UBE4B, a kind of E3 ubiquitin ligase enzyme, belongs to the U-box family that contains a characteristic U-box domain of about 70 amino acids, which directly recognizes specific substrates during the ubiquitination. UBE4B has a special E4 activity, which can drive polyubiquitin chain assembly with E1, E2, and E3. UBE4B plays a critical role in life processes such as embryonic development and neuron protection. It can also degrade a variety of substrates with important physiological functions, such as p53, EGFR, FEZ1 and Ataxin-3. UBE4B is related to the occurrence and development of cancer, neurodegeneration diseases and obesity. The study of UBE4B is of great significance for disease treatment and new drug development. This review demonstrated the structural characteristics, physiological functions, related diseases, and substrates of UBE4B, elaborating the research progress of UBE4B in the past two decades and providing theoretical guidance for further study of UBE4B.

Key words: ubiquitination, E3 ubiquitin ligases, UBE4B, U-box, E4

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