Loss of protein quality control gene UBR1 sensitizes Saccharomyces cerevisiae to the aminoglycoside hygromycin B.
Loss of protein quality control gene UBR1 sensitizes Saccharomyces cerevisiae to the aminoglycoside hygromycin B.
复制标题
蛋白质质量控制基因UBR1的丧失使酿酒酵母对氨基糖苷杂种霉素的敏感性敏感。
DOI：
10.33043/ff.6.1.76-83
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发表时间：
2020-10-26
期刊：
影响因子：
--
通讯作者：
Rubenstein EM
中科院分区：
文献类型：
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作者：
Runnebohm AM;Evans MD;Richardson AE;Turk SM;Olesen JB;Smaldino PJ;Rubenstein EM
ubr 1是一种保守的泛素连接酶，参与真核细胞中异常蛋白的降解。在Johanson-Blizzard综合征患者中发现人类酶发生突变。我们假设，Ubr 1是必要的最佳细胞适应性的异常和错误折叠的蛋白质丰度升高相关的条件。事实上，我们发现在模式真核微生物酿酒酵母中Ubr 1的缺失强烈地使细胞对潮霉素B敏感，潮霉素B通过引起核糖体A位点扭曲而降低翻译保真度。我们的研究结果与Ubr 1在蛋白质质量控制中的突出作用一致。我们推测Johanson-Blizzard综合征患者的疾病表现至少部分与Ubr 1功能丧失引起的蛋白质质量控制缺陷有关。
Ubr1 is a conserved ubiquitin ligase involved in the degradation of aberrant proteins in eukaryotic cells. The human enzyme is found mutated in patients with Johanson-Blizzard syndrome. We hypothesized that Ubr1 is necessary for optimal cellular fitness in conditions associated with elevated abundance of aberrant and misfolded proteins. Indeed, we found that loss of Ubr1 in the model eukaryotic microorganism Saccharomyces cerevisiae strongly sensitizes cells to hygromycin B, which reduces translational fidelity by causing ribosome A site distortion. Our results are consistent with a prominent role for Ubr1 in protein quality control. We speculate that disease manifestations in patients with Johanson-Blizzard syndrome are linked, at least in part, to defects in protein quality control caused by loss of Ubr1 function.