The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator
The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator
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DOI：
10.1074/jbc.272.21.13786
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发表时间：
1997-05-23
影响因子：
4.8
通讯作者：
Alexandraki, D
中科院分区：
文献类型：
--
作者：
Georgatsou, E;Mavrogiannis, LA;Alexandraki, D
Fre 1 p和Fre 2 p是铁还原酶，其占总质膜相关活性，铁吸收的先决条件，在酿酒酵母。这两个基因的转录诱导铁耗竭。在本通信中，我们提供了Fre 2 p也具有铜还原酶活性的证据，如先前对于Fre 1 p所示（Hassett，R.，和Kosman，D.J.（1995）J.Biol.Chem.270，128-134）。Fre 1 p和Fre 2 p酶都对铜吸收具有重要的功能意义，通过在fre 1 Delta、fre 2 Delta和fre 1 Delta fre 2 Delta突变株中铜调节的CUP 1和CTR 1 mRNA的积累进行监测。然而，即使在铁的存在下，铜耗尽也仅诱导Fre 1 p活性。这种差异铜依赖性调节Fre 1 p和Fre 2 p是在转录水平上的两个基因。我们已经表明，已知影响FRE 1基因表达的基础水平的Mac 1 p（Jungmann，J.，Reins，H.-一、李，J.，罗密欧，A.，哈西特河，Kosman，D.，和Jentsch，S.（1993）EMBO J. 12，5051-5056）解释了FRE 1的铜依赖性诱导和FRE 2基因的下调。最后，Mac 1 p转录激活功能本身由铜的可用性调节。
Fre1p and Fre2p are ferric reductases which account for the total plasma membrane associated activity, a prerequisite for iron uptake, in Saccharomyces cerevisiae. The two genes are transcriptionally induced by iron depletion. In this communication, we provide evidence that Fre2p has also cupric reductase activity, as has been previously shown for Fre1p (Hassett, R., and Kosman, D.J. (1995) J. Biol. Chem. 270, 128-134). Both Fre1p and Fre2p enzymes are functionally significant for copper uptake, as monitored by the accumulation of the copper-regulated CUP1 and CTR1 mRNAs in fre1 Delta, fre2 Delta, and fre1 Delta fre2 Delta mutant strains. However, only Fre1p activity is induced by copper depletion, even in the presence ofiron. This differential copper-dependent regulation of Fre1p and Fre2p is exerted at the transcriptional level of the two genes. We have shown that Mac1p, known to affect the basal levels of FRE1 gene expression (Jungmann, J., Reins, H.-A., Lee, J., Romeo, A., Hassett, R., Kosman, D., and Jentsch, S. (1993) EMBO J. 12, 5051-5056), accounts for both the copper-dependent induction of FRE1 and down-regulation of FRE2 gene. Finally, Mac1p transcriptional activation function is itself modulated by the availability of copper.