Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
Cell Death Differ. 2011 Sep;18(9):1393-402. doi: 10.1038/cdd.2011.16. Epub 2011 Mar 4.
Ubiquitin modification of many cellular proteins targets them for proteasomal degradation, but in addition can also serve non-proteolytic functions. Over the last years, a significant progress has been made in our understanding of how modification of the substrates of the ubiquitin system is regulated. However, little is known on how the ubiquitin system that is comprised of ∼1500 components is regulated. Here, we discuss how the biggest subfamily within the system, that of the E3 ubiquitin ligases that endow the system with its high specificity towards the numerous substrates, is regulated and in particular via self-regulation mediated by ubiquitin modification. Ligases can be targeted for degradation in a self-catalyzed manner, or through modification mediated by an external ligase(s). In addition, non-proteolytic functions of self-ubiquitination, for example activation of the ligase, of E3s are discussed.
泛素化修饰许多细胞蛋白可将其靶向蛋白酶体降解，但除此之外，泛素化修饰还具有非蛋白水解功能。在过去的几年中，人们对泛素系统底物修饰的调控机制有了显著的认识。然而，对于包含约 1500 个组件的泛素系统本身的调控机制却知之甚少。在这里，我们将讨论泛素系统中最大的亚家族，即 E3 泛素连接酶，它使系统对众多底物具有高度特异性，以及该亚家族是如何被调控的，特别是通过泛素化修饰的自我调控。连接酶可以通过自我催化的方式或通过外部连接酶介导的修饰来进行靶向降解。此外，还讨论了自泛素化的非蛋白水解功能，例如连接酶的激活。
