Yap5 Protein-regulated Transcription of the TYW1 Gene Protects Yeast from High Iron Toxicity
Yap5 Protein-regulated Transcription of the TYW1 Gene Protects Yeast from High Iron Toxicity
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DOI：
10.1074/jbc.m111.286666
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发表时间：
2011-11-04
影响因子：
4.8
通讯作者：
Kaplan, Jerry
中科院分区：
文献类型：
--
作者：
Li, Liangtao;Jia, Xuan;Kaplan, Jerry
芽殖酵母酿酒酵母通过诱导Yap5介导的转录来响应高胞质铁。我们确定了由Yap5调节的基因，以响应铁，并表明诱导的基因之一是TYW1，它编码一种铁硫簇酶，参与合成的wybutosine修饰的tRNA。TYW1缺失的菌株在标准酵母培养基中不显示表型。相反，TYW1的过表达导致细胞生长减少和铁调节子的诱导，导致高亲和力铁转运蛋白的表达增加。我们确定了S的一个极小整环。酿酒酵母Tyw1，足以诱导铁调节子。CCC1是一个液泡铁输入者，是一个受Yap5调控的基因，缺失CCC1或YAP5都会导致高铁敏感性。在Delta ccc1菌株中TYW1的缺失导致铁敏感性增加。Delta ccc1 Delta tyw1的铁敏感性增加可以通过铁硫簇酶的过表达来抑制。我们的结论是，Yap5介导的TYW1诱导提供保护，通过形成蛋白结合的铁硫簇消耗游离胞浆铁的高铁毒性。
The budding yeast Saccharomyces cerevisiae responds to high cytosolic iron by inducing Yap5-mediated transcription. We identified genes regulated by Yap5 in response to iron and show that one of the genes induced is TYW1, which encodes an iron-sulfur cluster enzyme that participates in the synthesis of wybutosine-modified tRNA. Strains deleted for TYW1 do not show a phenotype in standard yeast medium. In contrast, overexpression of TYW1 results in decreased cell growth and induction of the iron regulon, leading to increased expression of the high affinity iron transporters. We identified a minimal domain of S. cerevisiae Tyw1 that is sufficient to induce the iron regulon. CCC1, a vacuolar iron importer, is a Yap5-regulated gene, and deletion of either CCC1 or YAP5 resulted in high iron sensitivity. Deletion of TYW1 in a Delta ccc1 strain led to increased iron sensitivity. The increased iron sensitivity of Delta ccc1 Delta tyw1 could be suppressed by overexpression of iron-sulfur cluster enzymes. We conclude that the Yap5-mediated induction of TYW1 provides protection from high iron toxicity by the consumption of free cytosolic iron through the formation of protein-bound iron-sulfur clusters.