MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Nat Chem Biol. 2022 Aug;18(8):802-811. doi: 10.1038/s41589-022-01088-2. Epub 2022 Jul 27.
The ubiquitin system has become synonymous with the modification of lysine residues. However, the substrate scope and diversity of the conjugation machinery have been underappreciated, bringing us to an epoch in ubiquitin system research. The striking discoveries of metazoan enzymes dedicated toward serine and threonine ubiquitination have revealed the important role of nonlysine ubiquitination in endoplasmic reticulum-associated degradation, immune signaling and neuronal processes, while reports of nonproteinaceous substrates have extended ubiquitination beyond the proteome. Bacterial effectors that bypass the canonical ubiquitination machinery and form unprecedented linkage chemistry further redefine long-standing dogma. While chemical biology approaches have advanced our understanding of the canonical ubiquitin system, further study of noncanonical ubiquitination has been hampered by a lack of suitable tools. This Perspective aims to consolidate and contextualize recent discoveries and to propose potential applications of chemical biology, which will be instrumental in unraveling this new frontier of ubiquitin research.
泛素系统已成为赖氨酸残基修饰的代名词。然而，修饰酶的底物范围和多样性一直被低估，这使我们进入了泛素系统研究的新纪元。后生动物中专门作用于丝氨酸和苏氨酸的泛素化酶的惊人发现，揭示了非赖氨酸泛素化在内质网相关降解、免疫信号和神经元过程中的重要作用，而关于非蛋白类底物的报道则将泛素化作用扩展到了蛋白质组之外。能够绕过经典泛素化机制并形成前所未有的连接化学的细菌效应因子进一步颠覆了长期以来的定论。尽管化学生物学方法提高了我们对经典泛素系统的理解，但由于缺乏合适的工具，对非经典泛素化的进一步研究受到了阻碍。本观点旨在整合和阐述最近的发现，并提出化学生物学的潜在应用，这对于揭示泛素研究的这一新前沿至关重要。
