Biochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.
Biochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.
J Mol Biol. 2017 Apr 21;429(8):1097-1113. doi: 10.1016/j.jmb.2017.02.011. Epub 2017 Feb 21.
Phosphorylation and ubiquitination are pervasive post-translational modifications that impact all processes inside eukaryotic cells. The role of each modification has been studied for decades, and functional interplay between the two has long been demonstrated and even more widely postulated. However, our understanding of the molecular features that allow phosphorylation to control protein ubiquitination and ubiquitin to control phosphorylation has only recently begun to build. Here, we review examples of regulation between ubiquitination and phosphorylation, aiming to describe mechanisms at the molecular level. In general, these examples illustrate phosphorylation as a versatile switch throughout ubiquitination pathways, and ubiquitination primarily impacting kinase signalling in a more emphatic manner through scaffolding or degradation. Examples of regulation between these two processes are likely to grow even further as advances in molecular biology, proteomics, and computation allow a system-level understanding of signalling. Many new cases could involve similar principles to those described here, but the extensive co-regulation of these two systems leaves no doubt that they still have many surprises in store.
磷酸化和泛素化是普遍存在的翻译后修饰，影响真核细胞内的所有过程。几十年来，人们一直在研究每种修饰的作用，并且已经证明了两种修饰之间的功能相互作用，甚至更广泛地推测了这种相互作用。然而，我们对允许磷酸化控制蛋白质泛素化和泛素化控制磷酸化的分子特征的理解直到最近才开始建立。在这里，我们回顾了泛素化和磷酸化之间的调控实例，旨在描述分子水平上的机制。一般来说，这些例子表明磷酸化是泛素化途径中的一种通用开关，而泛素化主要通过支架或降解以更强调的方式影响激酶信号。随着分子生物学、蛋白质组学和计算的进步允许对信号进行系统级理解，这两种过程之间的调控例子可能会进一步增加。许多新的例子可能涉及与这里描述的类似的原则，但这两个系统的广泛共同调控无疑表明它们还有很多惊喜在等着我们。
