Kelsall Ian R
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, United Kingdom.
Front Mol Biosci. 2022 Sep 19;9:1008175. doi: 10.3389/fmolb.2022.1008175. eCollection 2022.
The post-translational modification of proteins with ubiquitin plays a central role in nearly all aspects of eukaryotic biology. Historically, studies have focused on the conjugation of ubiquitin to lysine residues in substrates, but it is now clear that ubiquitylation can also occur on cysteine, serine, and threonine residues, as well as on the N-terminal amino group of proteins. Paradigm-shifting reports of non-proteinaceous substrates have further extended the reach of ubiquitylation beyond the proteome to include intracellular lipids and sugars. Additionally, results from bacteria have revealed novel ways to ubiquitylate (and deubiquitylate) substrates without the need for any of the enzymatic components of the canonical ubiquitylation cascade. Focusing mainly upon recent findings, this review aims to outline the current understanding of non-lysine ubiquitylation and speculate upon the molecular mechanisms and physiological importance of this non-canonical modification.
蛋白质的泛素化翻译后修饰在真核生物生物学的几乎所有方面都起着核心作用。从历史上看，研究主要集中在泛素与底物中赖氨酸残基的结合，但现在很清楚，泛素化也可以发生在半胱氨酸、丝氨酸和苏氨酸残基上，以及蛋白质的N端氨基上。关于非蛋白质底物的范式转变报告进一步将泛素化的范围扩展到蛋白质组之外，包括细胞内脂质和糖类。此外，细菌研究结果揭示了在不需要经典泛素化级联反应的任何酶成分的情况下，对底物进行泛素化（和去泛素化）的新方法。本综述主要关注最近的研究结果，旨在概述目前对非赖氨酸泛素化的理解，并推测这种非经典修饰的分子机制和生理重要性。
