Chemical tools for studying conventional and non-conventional modes of ubiquitylation

我们的健康和幸福取决于我们体内细胞的正确功能。因此，我们必须彻底了解发生在它们体内的生化过程。正是这些过程在某些疾病中出现了缺陷，因此，掌握了它们的复杂性的知识，我们就可以合理地开发新的疗法，减轻它们的症状，甚至治愈它们。一种影响所有过程的细胞调节机制被称为蛋白质泛素化。蛋白质泛素化是指一种叫做泛素的小蛋白质附着在其他蛋白质上。这一步是由E3酶完成的。由于缺乏能够测量细胞中单个E3活性的研究技术，全面了解蛋白质泛素化的挑战就产生了。此外，我们现在对哪些蛋白质被泛素标记有很强的了解，但我们识别E3的能力非常困难，迫切需要新的工具。我们最近开发了一些令人兴奋和强大的技术，不仅可以测量细胞中单个E3s的活性，还可以同时测量数十个E3s的活性。这项技术将彻底改变我们理解E3s和蛋白质泛素化在正常和病变细胞中的作用的能力。

Our health and well-being are dependent on the correct functioning of the cells in our body. It is therefore imperative that we have a thorough understanding of the biochemical processes that take place within them. It is these processes that become faulty in certain diseases therefore being armed with the knowledge of their intricacies will place in a position where we can rationally develop new therapies that alleviate their symptoms of or even cure them.A cellular regulatory mechanism that affects all processes is known as protein ubiquitylation. Protein ubiquitylation involves the attachment of a small protein called ubiquitin to other proteins. This step is carried out by enzymes known as E3. Challenges with fully understanding protein ubiquitylation arise from a lack of research technologies that enable the activities of even a single E3 in a cell to be measured. Additionally, we now have strong knowledge about which proteins are tagged with ubiquitin but our ability to identify the E3 responsible is extremely difficult and new tools are urgently needed.We have recently developed some exciting and powerful technology that allows not only a single E3s activity in a cell to be measured, but the activity of tens of E3s to be measured simultaneously. This technology will revolutionise our ability to understand the roles of E3s and protein ubiquitylation in both normal and diseased cells.