Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, Taiwan.
Molecules. 2020 Nov 9;25(21):5200. doi: 10.3390/molecules25215200.
Ubiquitination is a versatile posttranslational modification that elicits signaling roles to impact on various cellular processes and disease states. The versatility is a result of the complexity of ubiquitin conjugates, ranging from a single ubiquitin monomer to polymers with different length and linkage types. Recent studies have revealed the abundant existence of branched ubiquitin chains in which one ubiquitin molecule is connected to two or more ubiquitin moieties in the same ubiquitin polymer. Compared to the homotypic ubiquitin chain, the branched chain is recognized or processed differently by readers and erasers of the ubiquitin system, respectively, resulting in a qualitative or quantitative alteration of the functional output. Furthermore, certain types of branched ubiquitination are induced by cellular stresses, implicating their important physiological role in stress adaption. In addition, the current chemical methodologies of solid phase peptide synthesis and expanding genetic code approach have been developed to synthesize different architectures of branched ubiquitin chains. The synthesized branched ubiquitin chains have shown their significance in understanding the topologies and binding partners of the branched chains. Here, we discuss the recent progresses on the detection, functional characterization and synthesis of branched ubiquitin chains as well as the future perspectives of this emerging field.
泛素化是一种多功能的翻译后修饰，通过影响各种细胞过程和疾病状态来发挥信号作用。这种多功能性是由于泛素缀合物的复杂性所致，其范围从单个泛素单体到具有不同长度和连接类型的聚合物。最近的研究揭示了支化泛素链的丰富存在，其中一个泛素分子在同一泛素聚合物中连接到两个或更多的泛素部分。与同型泛素链相比，分支链分别被泛素系统的读取器和擦除器以不同的方式识别或处理，从而导致功能输出的定性或定量改变。此外，某些类型的支化泛素化是由细胞应激诱导的，这表明它们在应激适应中具有重要的生理作用。此外，固相肽合成和扩展遗传密码方法的化学方法学已经被开发出来，以合成不同结构的支化泛素链。合成的支化泛素链在理解支化链的拓扑结构和结合伙伴方面显示出了其重要性。在这里，我们讨论了支化泛素链的检测、功能特征和合成方面的最新进展，以及这一新兴领域的未来展望。
