摘要
泛素折叠修饰因子1(ubiquitin-fold modifier 1,UFM1)是类泛素蛋白(ubiquitin-like modifier,UBL)家族的一员,存在于几乎所有的真核细胞中。UFM1对底物的修饰过程与泛素相似,即依次通过UBA5、UFC1和UFL1催化,共价接合在底物的赖氨酸残基上。而UFSP则负责切割UFM1的C端使之成熟,以及去除底物的UFM1修饰。UFM化修饰参与了内质网应激介导的细胞凋亡过程,对其具体作用机制的阐明需要鉴定到UFM1的修饰底物,但目前已经鉴定到UFM1的底物很少。大量研究尚聚焦于UFM修饰酶上。通过对UFM修饰酶和少量修饰底物的研究发现,UFM化修饰参与非酒精性肝病、细胞生成障碍性贫血、髋关节发育不良和神经系统疾病等的发生,以及乳腺癌细胞的增殖与转移和寄生虫的生长发育。本文将对UFM化修饰相关酶和修饰底物进行综述,总结UFM化修饰的生物学功能和在疾病发生发展中的作用。
Ubiquitin-fold modifier 1(UFM1) is a member of the ubiquitin-like modifier(UBL) family and exists in almost all eukaryotic cells. UFM1 shares similar modification processes with ubiquitin. UFM1 is cleaved by UFSP at the C-terminal for maturation and then catalyzed by UBA5, UFC1 and UFL1 successively to finally conjugate to specific lysine residue on the substrates covalently. UFSP is also responsible for deconjugating UFM1 from its substrates. The UFM1 modification is involved in the endoplasmic reticulum(ER) stress-mediated apoptosis, and the explanation to the detailed mechanism of this process requires the identification of UFM1 substrates. However, only a few UFM1 conjugated proteins have been identified so far, and most studies still focused on modification enzymes. It is reported that ufmylation participates in non-alcoholic steatohepatitis, hematopoietic anemia, hip dysplasia, neural system diseases, proliferation and metastasis of breast cancer cells, and the growth and metabolism of parasites. This review summarizes all enzymes and reported substrates of ufmylation, and discusses the biological functions of ufmylation in the development and progression of related diseases.
作者
张睿
陈亚兰
屠俊
ZHANG Rui;CHEN Ya-Lan;TU Jun(Shanghai Key Laboratory for Tumor Microenvironment and Inflammation , Department of Biochemistry and Molecular Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 , China;Grade 2015 Clinical Medicine ( 8-year program), School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 , China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2019年第3期229-239,共11页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金项目(No.31600664
81700701)
中央高校基本科研业务费专项资金资助~~
关键词
泛素折叠修饰因子1
UFM化修饰
内质网应激
ubiquitin-fold modifier 1 ( UFM 1)
UFMylation
endoplasmic reticulum stress( ERS)