Uracil-Induced Down-Regulation of the Yeast Uracil Permease
Uracil-Induced Down-Regulation of the Yeast Uracil Permease
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DOI：
10.1128/jb.181.6.1793-1800.1999
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发表时间：
1999-03
影响因子：
3.2
通讯作者：
K. Séron;M. Blondel;R. Haguenauer‐Tsapis;C. Volland
中科院分区：
文献类型：
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作者：
K. Séron;M. Blondel;R. Haguenauer‐Tsapis;C. Volland
摘要 在酿酒酵母中，FUR4 编码的尿嘧啶通透酶催化嘧啶补救途径的第一步。尿嘧啶的可用性对其自身的运输具有负面调节作用。尿嘧啶导致尿嘧啶通透酶水平降低，部分是通过以启动子无关的方式降低FUR4 mRNA水平，可能是通过增加其不稳定性。尿嘧啶的进入还通过促进通透酶的高效率泛素化来触发现有通透酶的更快速降解，从而发出其内化的信号。细胞内尿嘧啶与通透酶的直接结合可能参与了这种反馈调节，因为通透酶的行为在不能将细胞内尿嘧啶转化为UMP的突变细胞中是相似的。我们使用泛素化步骤受损的细胞来证明尿嘧啶的添加会快速抑制尿嘧啶转运。这可能是从质膜去除渗透酶之前的第一个反应。在不利条件下观察到类似的尿嘧啶摄取下调，涉及多个过程，主要对应于核糖体细胞含量的减少。这些结果表明，外源或分解代谢来源的尿嘧啶下调同源通透酶，以防止细胞内过量的尿嘧啶衍生核苷酸的积累。
ABSTRACT In Saccharomyces cerevisiae theFUR4-encoded uracil permease catalyzes the first step of the pyrimidine salvage pathway. The availability of uracil has a negative regulatory effect upon its own transport. Uracil causes a decrease in the level of uracil permease, partly by decreasing theFUR4 mRNA level in a promoter-independent fashion, probably by increasing its instability. Uracil entry also triggers more rapid degradation of the existing permease by promoting high efficiency of ubiquitination of the permease that signals its internalization. A direct binding of intracellular uracil to the permease is possibly involved in this feedback regulation, as the behavior of the permease is similar in mutant cells unable to convert intracellular uracil into UMP. We used cells impaired in the ubiquitination step to show that the addition of uracil produces rapid inhibition of uracil transport. This may be the first response prior to the removal of the permease from the plasma membrane. Similar down-regulation of uracil uptake, involving several processes, was observed under adverse conditions mainly corresponding to a decrease in the cellular content of ribosomes. These results suggest that uracil of exogenous or catabolic origin down-regulates the cognate permease to prevent buildup of excess intracellular uracil-derived nucleotides.