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首页> 美国卫生研究院文献>Molecular and Cellular Biology >trans Repression of the Human Metallothionein IIA Gene Promoter by PZ120 a Novel 120-Kilodalton Zinc Finger Protein
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trans Repression of the Human Metallothionein IIA Gene Promoter by PZ120 a Novel 120-Kilodalton Zinc Finger Protein

机译：一种新型120-千达锌锌指蛋白PZ120反式抑制人类金属硫蛋白IIA基因启动子

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摘要

Metallothioneins are small, highly conserved, cysteine-rich proteins that bind a variety of metal ions. They are found in virtually all eukaryotic organisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as binding sites for trans-acting factors such as Sp1, AP1, AP2, AP4, and the glucocorticoid receptor, the hMTIIA promoter contains eight consensus metal response element sequences. We report here the cloning of a novel zinc finger protein with a molecular mass of 120 kDa (PZ120) that interacts specifically with the hMTIIA transcription initiation site. The PZ120 protein is ubiquitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcription factors. Intriguingly, we found that a region of PZ120 outside of the zinc finger domain can bind specifically to the hMTIIA DNA. Using transient-transfection analysis, we found that PZ120 repressed transcription of the hMTIIA promoter. These results suggest that the hMTIIA gene is regulated by an additional negative regulator that has not been previously described.
机译：金属硫蛋白是小的，高度保守的，富含半胱氨酸的蛋白质，可结合多种金属离子。它们实际上存在于所有真核生物中，并且主要在转录水平受到调控。在人类中，主要的金属硫蛋白基因是hMTIIA，占培养的人类细胞中表达的所有金属硫蛋白的50％。 hMTIIA启动子非常复杂。除了充当反式作用因子（例如Sp1，AP1，AP2，AP4和糖皮质激素受体）结合位点的顺式作用DNA序列外，hMTIIA启动子还包含八个共有金属反应元件序列。我们在这里报告的分子质量为120 kDa（PZ120）的新型锌指蛋白的克隆与hMTIIA转录起始位点特异性相互作用。 PZ120蛋白在大多数组织中普遍表达，并具有以前在几种锌指转录因子中发现的保守的痘病毒和锌指（POZ）基序。有趣的是，我们发现锌指结构域之外的PZ120区域可以特异性结合hMTIIA DNA。使用瞬时转染分析，我们发现PZ120抑制了hMTIIA启动子的转录。这些结果表明，hMTIIA基因受以前未描述的其他负调控因子的调控。

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