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Abstract：
Post-translational modification of proteins by ubiquitin is required for nearly all aspects of eukaryotic cell function. The numerous targets of ubiquitylation, and variety of ubiquitin modifications, are often likened to a code, where the ultimate messages are diverse responses to target ubiquitylation. E1, E2, and E3 multiprotein enzymatic assemblies modify specific targets and thus function as messengers. Recent advances in chemical and protein tools have revolutionized our ability to explore the ubiquitin system, through enabling new high-throughput screening methods, matching ubiquitylation enzymes with their cellular targets, revealing intricate allosteric mechanisms regulating ubiquitylating enzymes, facilitating structural revelation of transient assemblies determined by multivalent interactions, and providing new paradigms for inhibiting and redirecting ubiquitylation in vivo as new therapeutics. Here we discuss the development of methods that control, disrupt, and extract the flow of information across the ubiquitin system and have enabled elucidation of the underlying molecular and cellular biology.
摘要：
通过泛素对蛋白质的翻译后修饰对于真核细胞功能的几乎所有方面都是必需的。泛素化的众多目标，和各种泛素修饰，通常被比作代码，其中最终的信息是对目标泛素化的不同反应。E1，E2和E3多蛋白酶促组装体修饰特定靶标，因此充当信使。化学和蛋白质工具的最新进展彻底改变了我们探索泛素系统的能力，通过启用新的高通量筛选方法，将泛素化酶与它们的细胞靶标相匹配，揭示了调节泛素化酶的复杂变构机制，促进由多价相互作用决定的瞬态装配的结构揭示，并为体内抑制和重定向泛素化提供了新的范例作为新疗法。在这里，我们讨论控制方法的发展，中断，并提取泛素系统中的信息流，并能够阐明潜在的分子和细胞生物学。
