Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
Department of Biochemistry, Vanderbilt University, Nashville, United States.
Elife. 2020 Oct 19;9:e58155. doi: 10.7554/eLife.58155.
Ubiquitination regulates many different cellular processes, including protein quality control, membrane trafficking, and stress responses. The diversity of ubiquitin functions in the cell is partly due to its ability to form chains with distinct linkages that can alter the fate of substrate proteins in unique ways. The complexity of the ubiquitin code is further enhanced by post-translational modifications on ubiquitin itself, the biological functions of which are not well understood. Here, we present genetic and biochemical evidence that serine 57 (Ser57) phosphorylation of ubiquitin functions in stress responses in , including the oxidative stress response. We also identify and characterize the first known Ser57 ubiquitin kinases in yeast and human cells, and we report that two Ser57 ubiquitin kinases regulate the oxidative stress response in yeast. These studies implicate ubiquitin phosphorylation at the Ser57 position as an important modifier of ubiquitin function, particularly in response to proteotoxic stress.
泛素化调节许多不同的细胞过程，包括蛋白质质量控制、膜运输和应激反应。泛素在细胞中的功能多样性部分归因于它能够形成具有不同连接的链，这些链可以以独特的方式改变底物蛋白的命运。泛素自身的翻译后修饰进一步增强了泛素密码的复杂性，但其生物学功能尚不清楚。在这里，我们提供了遗传和生化证据，表明泛素丝氨酸 57 位（Ser57）的磷酸化在酵母中的应激反应中发挥作用，包括氧化应激反应。我们还鉴定并表征了酵母和人类细胞中第一个已知的 Ser57 泛素激酶，并报告了两个 Ser57 泛素激酶调节酵母的氧化应激反应。这些研究表明，Ser57 位泛素磷酸化是泛素功能的一个重要调节剂，特别是在应对蛋白毒性应激时。
