Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast.

Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast.
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DOI:
10.1074/jbc.m104987200
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发表时间:
2001-09-07
影响因子:
4.8
通讯作者:
Camadro, JM
Camadro, JM
中科院分区:
生物学2区
文献类型:
--
作者:
Blaiseau, PL;Lesuisse, E;Camadro, JM

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酵母,酿酒酵母,含有转录激活因子,Aft1p,调节高亲和力铁转运系统基因的转录。本报告描述了Aft2p的性质,Aft2p是一种与Aft1p同源性为39%的蛋白质。Aft2p被发现激活转录。Aft2p的过量产生激活AFT 1靶基因FET 3的转录。双aft1aft2突变体不能在缺铁条件下生长。因为fet3突变体没有表现出这种缺陷,这种缺陷不仅是由于铁转运的错误调节引起的,而且还涉及细胞对铁的利用缺陷。aft1细胞不能在有氧条件下在含有棉子糖作为唯一碳源的平板上生长。不能在棉子糖上生长不是由于细胞铁含量太低而不能维持呼吸代谢,因为aft1突变体的耗氧量显示它们的呼吸活性比对照高2倍。双aft1aft2突变体还具有许多与氧化应激相关的表型,如H2O2超敏反应、氧依赖性铜毒性和氧依赖性甲硫氨酸营养缺陷型,这些表型在厌氧条件下受到抑制。这些结果表明Aft2p和Aft1p在控制与酵母抗氧化应激相关的铁调节途径中具有重叠作用。
The yeast, Saccharomyces cerevisiae, contains a transcription activator, Aft1p, that regulates the transcription of the high affinity iron transport system genes. This report describes the properties of Aft2p, a protein 39% homologous to Aft1p. Aft2p was found to activate transcription. Overproduction of Aft2p activates the transcription of the AFT1 target gene FET3. The double aft1aft2 mutant was unable to grow in iron-deprived conditions. Because a fet3 mutant does not show this deficiency, the defect is not solely caused by mis-regulation of iron transport but also involves defective iron use by the cells. The aft1 cells were unable to grow in aerobic conditions on plates containing raffinose as the sole carbon source. The inability to grow on raffinose is not caused by the cell iron content being too low to sustain respiratory metabolism, because the oxygen consumption of aft1 mutants showed that their respiratory activity is 2-fold higher than that of controls. The double aft1aft2 mutant also has many phenotypes related to oxidative stress such as H2O2 hypersensitivity, oxygen-dependent copper toxicity, and oxygen-dependent methionine auxotrophy, which are suppressed in anaerobiosis. These results suggest that Aft2p and Aft1p have overlapping roles in the control of iron-regulated pathway(s) connected to oxidative stress resistance in yeast.