A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe
A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe
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DOI：
10.1074/jbc.274.51.36252
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发表时间：
1999-12-17
影响因子：
4.8
通讯作者：
Thiele, DJ
中科院分区：
文献类型：
--
作者：
Labbé, S;Peña, MMO;Thiele, DJ
铜和铁作为多种关键细胞酶的催化辅因子发挥着重要作用。对酵母的研究表明，铁运输机械的正确组装和功能完全依赖于铜的获取。我们从粟酒裂殖酵母中克隆了高亲和力铜转运蛋白 (Ctr4) 和铜感应转录因子 (Cuf1) 的基因。有趣的是，Ctr4 和假定的人类高亲和力铜转运蛋白 hCtr1 的一级结构表明，它们源自功能冗余但结构不同的酿酒酵母 Ctr1 和 Ctr3 铜转运蛋白的融合。此外，虽然Cuf1在铜饥饿条件下激活ctr4(+)基因表达，但在这些相同条件下Cuf1直接抑制编码铁转运机制成分的基因的表达。这些研究确定了铜转运模块融合的进化步骤，并描述了在必需铜辅助因子稀缺的条件下铜感应因子直接抑制铁摄取基因表达的机制。
Copper and iron serve essential functions as catalytic co-factors in a wide variety of critical cellular enzymes. Studies in yeast have demonstrated an absolute dependence upon copper acquisition for proper assembly and function of the iron transport machinery. We have cloned genes for a high affinity copper transporter (Ctr4) and copper-sensing transcription factor (Cuf1) from Schizosaccharomyces pombe. Interestingly, the primary structure of Ctr4 and a putative human high affinity copper transport protein, hCtr1, suggests that they are derived from a fusion of the functionally redundant but structurally distinct Ctr1 and Ctr3 copper transporters from Saccharomyces cerevisiae. Furthermore, although Cuf1 activates ctr4(+) gene expression under copper starvation conditions, under these same conditions Cuf1 directly represses expression of genes encoding components of the iron transport machinery. These studies have identified an evolutionary step in which copper transport modules have been fused, and describe a mechanism by which a copper-sensing factor directly represses expression of the iron uptake genes under conditions in which the essential copper co-factor is scarce.