Leestemaker Yves, Ovaa Huib
Department of Chemical Immunology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Department of Chemical Immunology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Drug Discov Today Technol. 2017 Dec;26:25-31. doi: 10.1016/j.ddtec.2017.11.006. Epub 2017 Nov 26.
Ubiquitin is a 76-amino acid regulatory protein involved in many important cellular processes. Ubiquitin can be attached to other proteins at either a lysine residue or to the N-terminus by the consecutive actions of E1, E2, and E3 enzymes. Ubiquitin can also be attached to itself, resulting in poly-ubiquitin chains. Ubiquitination affects substrate proteins in different ways, for example by resulting in degradation of the substrate protein by the 26S proteasome. Ubiquitination can be reversed by deubiquitinating enzymes, which either trim or remove ubiquitin chains from proteins. Many proteins involved in either the ubiquitination, deubiquitination or degradation of proteins are implicated in human diseases and are currently under investigation as potential drug targets.
泛素是一种由76个氨基酸组成的调节蛋白,参与许多重要的细胞过程。通过E1、E2和E3酶的连续作用,泛素可以在赖氨酸残基处或N端与其他蛋白质连接。泛素也可以自身连接,形成多聚泛素链。泛素化以不同方式影响底物蛋白,例如导致底物蛋白被26S蛋白酶体降解。去泛素化酶可以逆转泛素化,这些酶可以从蛋白质上修剪或去除泛素链。许多参与蛋白质泛素化、去泛素化或降解的蛋白质与人类疾病有关,目前正在作为潜在的药物靶点进行研究。