Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Amino Acids. 2012 Sep;43(3):1049-60. doi: 10.1007/s00726-012-1286-y. Epub 2012 Jul 22.
Ubiquitin signaling plays an essential role in controlling cellular processes in eukaryotes, and the impairment of ubiquitin regulation contributes to the pathogenesis of a wide range of human diseases. During the last decade, mass spectrometry-based proteomics has emerged as an indispensable approach for identifying the ubiquitinated proteome (ubiquitinome), ubiquitin modification sites, the linkages of complex ubiquitin chains, as well as the interactome of ubiquitin enzymes. In particular, implementation of quantitative strategies allows the detection of dynamic changes in the ubiquitinome, enhancing the ability to differentiate between function-relevant protein targets and false positives arising from biological and experimental variations. The profiling of total cell lysate and the ubiquitinated proteome in the same sets of samples has become a powerful tool, revealing a subset of substrates that are modulated by specific physiological and pathological conditions, such as gene mutations in ubiquitin signaling. This strategy is equally useful for dissecting the pathways of ubiquitin-like proteins.
泛素信号在真核生物中控制细胞过程中发挥着重要作用，而泛素调节的损伤导致了广泛的人类疾病的发病机制。在过去的十年中，基于质谱的蛋白质组学已经成为鉴定泛素化蛋白质组（泛素组）、泛素修饰位点、复杂泛素链的连接以及泛素酶相互作用组的不可或缺的方法。特别是，定量策略的实施可以检测泛素组的动态变化，提高区分功能相关蛋白靶标和生物和实验变异产生的假阳性的能力。在相同的样本组中对总细胞裂解物和泛素化蛋白质组进行分析已成为一种强大的工具，揭示了受特定生理和病理条件（如泛素信号中的基因突变）调节的底物亚组。这种策略同样可用于剖析泛素样蛋白的途径。
