Department of Oncology, University of Cambridge, Hutchison/Medical Research Council (MRC) Research Centre, Cambridge, UK.
Int J Biochem Cell Biol. 2013 Aug;45(8):1833-42. doi: 10.1016/j.biocel.2013.05.026. Epub 2013 May 31.
Post-translational protein modifications initiate, regulate, propagate and terminate a wide variety of processes in cells, and in particular, ubiquitylation targets substrate proteins for degradation, subcellular translocation, cell signaling and multiple other cellular events. Modification of substrate proteins is widely observed to occur via covalent linkages of ubiquitin to the amine groups of lysine side-chains. However, in recent years several new modes of ubiquitin chain attachment have emerged. For instance, covalent modification of non-lysine sites in substrate proteins is theoretically possible according to basic chemical principles underlying the ubiquitylation process, and evidence is building that sites such as the N-terminal amine group of a protein, the hydroxyl group of serine and threonine residues and even the thiol groups of cysteine residues are all employed as sites of ubiquitylation. However, the potential importance of this "non-canonical ubiquitylation" of substrate proteins on sites other than lysine residues has been largely overlooked. This review aims to highlight the unusual features of the process of non-canonical ubiquitylation and the consequences of these events on the activity and fate of a protein.
蛋白质翻译后修饰启动、调节、扩展和终止细胞中的各种过程，特别是泛素化将底物蛋白靶向降解、亚细胞易位、细胞信号转导和多种其他细胞事件。广泛观察到通过将泛素共价连接到赖氨酸侧链的氨基基团来修饰底物蛋白。然而，近年来出现了几种新的泛素链连接方式。例如，根据泛素化过程的基本化学原理，底物蛋白中非赖氨酸位点的共价修饰在理论上是可能的，并且有证据表明，蛋白质的 N-末端氨基、丝氨酸和苏氨酸残基的羟基，甚至半胱氨酸残基的巯基都被用作泛素化的位点。然而，除赖氨酸残基以外的底物蛋白的这种“非典型泛素化”在蛋白质活性和命运上的潜在重要性在很大程度上被忽视了。本综述旨在强调非典型泛素化过程的独特特征，以及这些事件对蛋白质活性和命运的影响。
