Department of Molecular Cell Biology, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0371 Oslo, Norway; Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0371 Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0371 Oslo, Norway.
J Biol Chem. 2019 Dec 6;294(49):18784-18795. doi: 10.1074/jbc.RA119.009721. Epub 2019 Nov 1.
Post-translational modification by small ubiquitin-like modifier (Sumo) regulates many cellular processes, including the adaptive response to various types of stress, referred to as the Sumo stress response (SSR). However, it remains unclear whether the SSR involves a common set of core proteins regardless of the type of stress or whether each particular type of stress induces a stress-specific SSR that targets a unique, largely nonoverlapping set of Sumo substrates. In this study, we used MS and a Gene Ontology approach to identify differentially sumoylated proteins during heat stress, hyperosmotic stress, oxidative stress, nitrogen starvation, and DNA alkylation in cells. Our results indicate that each stress triggers a specific SSR signature centered on proteins involved in transcription, translation, and chromatin regulation. Strikingly, whereas the various stress-specific SSRs were largely nonoverlapping, all types of stress tested here resulted in desumoylation of subunits of RNA polymerase III, which correlated with a decrease in tRNA synthesis. We conclude that desumoylation and subsequent inhibition of RNA polymerase III constitutes the core of all stress-specific SSRs in yeast.
小泛素样修饰物（Sumo）介导的翻译后修饰调控许多细胞过程，包括对各种类型应激的适应性反应，即所谓的Sumo应激反应（SSR）。然而，目前尚不清楚SSR是否涉及一组共同的核心蛋白，而与应激类型无关，或者每种特定类型的应激是否会诱导一种应激特异性的SSR，该SSR靶向一组独特的、基本不重叠的Sumo底物。在本研究中，我们使用质谱（MS）和基因本体论方法来鉴定细胞在热应激、高渗应激、氧化应激、氮饥饿和DNA烷基化过程中差异SUMO化的蛋白质。我们的结果表明，每种应激都会触发一个特定的SSR特征，该特征以参与转录、翻译和染色质调控的蛋白质为中心。引人注目的是，虽然各种应激特异性SSR在很大程度上不重叠，但此处测试的所有应激类型均导致RNA聚合酶III亚基的去SUMO化，这与tRNA合成减少相关。我们得出结论，去SUMO化以及随后对RNA聚合酶III的抑制构成了酵母中所有应激特异性SSR的核心。
