摘要
神经前体表达发育下调蛋白8(neural precursor cell-expressed developmentally downregulated 8,Nedd8)是一种类泛素蛋白,其参与蛋白质修饰的作用机制与泛素高度相似,即通过与底物的赖氨酸残基共价结合,从而对底物进行Neddylation修饰。Neddylation修饰可调控多种重要的生命活动,如细胞周期和免疫应答等。Nedd8蛋白酶1(Nedd8 protease 1, NEDP1)是隶属于小类泛素修饰物特异性蛋白酶家族(small ubiquitin-like modifier specific protease family, Ulp/Senp family)家族的半胱氨酸蛋白酶,可以特异性去除底物与Nedd8的共价结合,例如,NEDP1能够去除p53、鼠双微体蛋白(murine double min-utes 2 protein, Mdm2)、smad泛素化调节因子1(smad ubiquitylation regulatory factor 1, Smurf1)等多个蛋白质的Neddylation修饰,进而调节Neddylation修饰蛋白的生物学功能。临床研究表明,NEDP1与肿瘤的发生发展密切相关,包括肺癌、结肠癌、胶质母细胞瘤等,另外,NEDP1还参与成骨发育异常、神经退行性疾病、血管炎症等病变过程。本文对NEDP1蛋白的结构,调控Neddylation通路的作用模式和NEDP1作用底物的进展进行总结,以期为肿瘤等相关疾病的诊断和治疗提供参考。
Neural precursor cell-expressed developmentally downregulated 8(Nedd8), a ubiquitin-like protein, whose mechanism of action involved in protein modification, is highly similar to ubiquitin, that is,by covalently binding to the lysine residue of the substrate, the substrate is subjected to Neddylation modification. Neddylation modification can regulate a variety of important life activities, such as cell cycle and immune response. Nedd8 protease 1(NEDP8) is a cysteine protease belonging to small ubiquitin-like modifier specific protease family that specifically removes the covalent attachment of substrates to Nedd8, for example,NEDP1 is able to remove Neddylation modifications of multiple proteins such as p53, murine double minutes2 protein(Mdm2) and smad ubiquitylation regulatory factor 1(Smurf1) to regulate the biological function of Neddylation-modified proteins. Clinical studies have shown that NEDP1 is closely related to the occurrence and development of tumors, including lung cancer, colon cancer, glioblastoma, etc. In addition, NEDP1 is also involved in osteogenic dysplasia, neurodegenerative disease, vascular inflammation and other pathological processes. In this paper, we summarize the structure of NEDP1 protein, the mode of action of regulating the Neddylation pathway and the progress of NEDP1 substrate, in order to provide reference for the diagnosis and treatment of tumor and other related diseases.
引文
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