EUKARYOTIC GENE REGULATION AND FUNCTION--THE METALLOTHIONEIN SYSTEM

金属离子可以激活和抑制真核基因表达。 在 酵母细胞，铜激活金属硫蛋白基因表达的直接 与ACE1转录因子的DNA结合结构域相互作用。 我们已经获得证据表明ACE 1的11个关键半胱氨酸残基 被组织成两个亚群，与不同的区域相互作用， 上游激活序列。 Cu还抑制了 几个基因参与铜的吸收和利用，包括细胞 表面还原酶基因FRE1。 我们发现并克隆了一种新的 调节因子ACU1参与了这一抑制途径。 ACU1 与ACE1弱同源，并含有富含半胱氨酸的基序 铜结合蛋白的特征。因此，我们所研究的每一种蛋白质 已被证明是至关重要的铜稳态酵母似乎承担 共同的结构元素，我们称之为“铜拳”。

Metal ions can both activate and repress eukaryotic gene expression. In yeast cells, Cu activates metallothionein gene expression by directly interacting with the DNA-binding domain of the ACE1 transcription factor. We have obtained evidence that the 11 critical cysteine residues of ACE1 are organized into two subclusters that interact with distinct regions of the upstream activation sequence. Cu also represses the activity of several genes involved in Cu uptake and utilization, including the cell surface reductase gene FRE1. We have identified and cloned a new regulatory factor, ACU1, that is involved in this repression pathway. ACU1 is weakly homologous to ACE1, and contains a cysteine-rich motif characteristic of Cu-binding proteins. Thus, each of the proteins that we have shown to be critical for Cu homeostasis in yeast appears to bear a common structural element, which we have dubbed the "Cu fist".