Brugnera E, Georgiev O, Radtke F, Heuchel R, Baker E, Sutherland G R, Schaffner W
Institut für Molekularbiologie II, Universität Zürich, Switzerland.
Nucleic Acids Res. 1994 Aug 11;22(15):3167-73. doi: 10.1093/nar/22.15.3167.
Metallothioneins (MTs) are small cysteine-rich proteins that bind heavy metal ions such as zinc, cadmium and copper with high affinity, and have been functionally implicated in heavy metal detoxification and radical scavenging. Transcription of metallothioneins genes is induced by exposure of cells to heavy metals. This induction is mediated by metal-responsive promoter elements (MREs). We have previously cloned the cDNA of an MRE-binding transcription factor (MTF-1) from the mouse. Here we present the human cDNA equivalent of this metal-regulatory factor. Human MTF-1 is a protein of 753 amino acids with 93% amino acid sequence identity to mouse MTF-1 and has an extension of 78 amino acids at the C-terminus without counterpart in the mouse. The factors of both species have the same overall structure including six zinc fingers in the DNA binding domain. We have physically mapped the human MTF-1 gene to human chromosome 1 where it localizes to the short arm in the region 1p32-34, most likely 1p33. Both human and mouse MTF-1 when produced in transfected mammalian cells strongly bind to a consensus MRE of metallothionein promoters. However, human MTF-1 is more effective than the mouse MTF-1 clone in mediating zinc-induced transcription.
金属硫蛋白（MTs）是一类富含半胱氨酸的小蛋白，能与锌、镉和铜等重金属离子高亲和力结合，在重金属解毒和自由基清除中发挥功能作用。金属硫蛋白基因的转录由细胞暴露于重金属所诱导。这种诱导由金属反应性启动子元件（MREs）介导。我们之前从小鼠中克隆了一种MRE结合转录因子（MTF-1）的cDNA。在此我们展示了这种金属调节因子的人类cDNA对应物。人类MTF-1是一种由753个氨基酸组成的蛋白质，与小鼠MTF-1的氨基酸序列同一性为93%，且在C端有一段78个氨基酸的延伸，这在小鼠中没有对应物。两种物种的因子具有相同的整体结构，包括在DNA结合域中的六个锌指。我们已将人类MTF-1基因物理定位到人类1号染色体，它定位于短臂1p32 - 34区域，最可能是1p33。当在转染的哺乳动物细胞中产生时，人类和小鼠的MTF-1都能强烈结合金属硫蛋白启动子的共有MRE。然而，在介导锌诱导的转录方面，人类MTF-1比小鼠MTF-1克隆更有效。
