Department of Pharmacology, University of Washington, Seattle, WA, United States of America.
PLoS Genet. 2019 Apr 22;15(4):e1008115. doi: 10.1371/journal.pgen.1008115. eCollection 2019 Apr.
Environmental stressors can severely perturb cellular homeostasis and compromise viability. To cope with environmental stressors, eukaryotes have developed distinct signaling programs that allow for adaptation during different stress conditions. These programs often require a host of post-translational modifications that alter proteins to elicit appropriate cellular responses. One crucial protein modifier during stress is the small ubiquitin-like modifier SUMO. In many cases, however, the functions of stress dependent protein SUMOylation remain unclear. Previously, we showed that the conserved Saccharomyces cerevisiae Cyc8-Tup1 transcriptional corepressor complex undergoes transient hyperosmotic stress-induced SUMOylation and inclusion formation, which are important for appropriate regulation of hyperosmotic-stress genes. Here, we show the osmostress-responsive MAP kinase Hog1 regulates Cyc8 SUMOylation and inclusion formation via its role in the transcriptional activation of glycerol biosynthesis genes. Mutations that ablate Cyc8 SUMOylation can partially rescue the osmosensitivity of hog1Δ cells, and this is facilitated by inappropriate derepression of glycerol-biosynthesis genes. Furthermore, cells specifically unable to synthesize the osmolyte glycerol cause transient Cyc8 SUMOylation and inclusions to persist, indicating a regulatory role for glycerol to reestablish the basal state of Cyc8 following adaptation to hyperosmotic stress. These observations unveil a novel intersection between phosphorylation and SUMOylation networks, which are critical for shifting gene expression and metabolic programs during stress adaptation.
环境胁迫因素会严重扰乱细胞内稳态并损害细胞活力。为了应对环境胁迫因素，真核生物已经开发出不同的信号转导途径，以便在不同的胁迫条件下进行适应。这些途径通常需要大量的翻译后修饰，这些修饰可以改变蛋白质，从而引发适当的细胞反应。在应激过程中，一种重要的蛋白质修饰酶是小泛素样修饰物 SUMO。然而，在许多情况下，应激依赖性蛋白质 SUMO 化的功能仍然不清楚。之前，我们发现保守的酿酒酵母 Cyc8-Tup1 转录共抑制复合物会经历瞬时高渗胁迫诱导的 SUMO 化和包含体形成，这对于适当调节高渗胁迫基因至关重要。在这里，我们表明，渗透压应激响应的 MAP 激酶 Hog1 通过其在甘油生物合成基因转录激活中的作用，调节 Cyc8 的 SUMO 化和包含体形成。消除 Cyc8 SUMO 化的突变可以部分挽救 hog1Δ 细胞的渗透压敏感性，这是由于甘油生物合成基因的不当去抑制。此外，细胞特异性地不能合成渗透剂甘油会导致 Cyc8 的瞬时 SUMO 化和包含体持续存在，这表明甘油在适应高渗胁迫后重新建立 Cyc8 基础状态方面具有调节作用。这些观察结果揭示了磷酸化和 SUMO 化网络之间的一个新的交叉点，这对于在应激适应过程中转移基因表达和代谢途径至关重要。
