Despite its central role in protein degradation little is known about the molecular mechanisms that sense, maintain, and regulate steady state concentration of ubiquitin in the cell. Here, we describe a novel mechanism for regulation of ubiquitin homeostasis that is mediated by phosphorylation of ubiquitin at the Ser57 position. We find that loss of Ppz phosphatase activity leads to defects in ubiquitin homeostasis that are at least partially attributable to elevated levels of Ser57 phosphorylated ubiquitin. Phosphomimetic mutation at the Ser57 position of ubiquitin conferred increased rates of endocytic trafficking and ubiquitin turnover. These phenotypes are associated with bypass of recognition by endosome-localized deubiquitylases - including Doa4 which is critical for regulation of ubiquitin recycling. Thus, ubiquitin homeostasis is significantly impacted by the rate of ubiquitin flux through the endocytic pathway and by signaling pathways that converge on ubiquitin itself to determine whether it is recycled or degraded in the vacuole.

中文翻译：

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酵母中的泛素周转和内吞运输受泛素 Ser57 磷酸化的调节

尽管它在蛋白质降解中发挥核心作用，但对于感知、维持和调节细胞中泛素稳态浓度的分子机制知之甚少。在这里，我们描述了一种调节泛素稳态的新机制，该机制由 Ser57 位置的泛素磷酸化介导。我们发现 Ppz 磷酸酶活性的丧失导致泛素稳态缺陷，这至少部分归因于 Ser57 磷酸化泛素水平升高。遍在蛋白 Ser57 位置的拟磷突变使内吞运输和遍在蛋白周转率增加。这些表型与内体定位的去泛素酶（包括对泛素循环调节至关重要的 Doa4）的识别绕过有关。因此，