EUKARYOTIC GENE REGULATION AND FUNCTION--THE METALLOTHIONEIN SYSTEM

真核基因调控与功能--金属硫蛋白系统

• 批准号: 3916290
• 负责人: D H HAMER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916290
• 关键词: Saccharomyces; copper; developmental genetics; eukaryote; gene expression; genetic manipulation; genetic regulation; genetic transcription; homeostasis; metallothionein; molecular cloning; molecular genetics; nucleic acid sequence; point mutation; transfection

The metallothioneins provide a useful model to study how eukaryotic genes are regulated and how the gene products allow cellular adaptation and homeostasis. Using the simple unicellular eukaryote Saccharomyces cerevisiae, a detailed analysis of the cis-acting control sequences that regulate metallothionein gene transcription in response to copper has been carried out. In addition, a trans- acting gene required for transcriptional induction has been identified and cloned. We propose that regulation of the yeast gene occurs through the interaction of both positive and negative factors. Structure-function relationships of yeast metallothionein have been studied by a combination of site-specific mutagenesis and biophysical techniques and residues critical to the functional activity of this protein have been identified. Metallothionein gene regulation in the more complex cells of the mouse has also been analyzed. Systematic point mutagenesis of the control region reveals different residues required for induction and for efficient transcription. Two factors that bind to these regions have been identified and separated.

金属硫蛋白为研究真核生物 基因是受调控的，以及基因产物如何使细胞 适应和动态平衡。利用简单的单细胞真核生物 酿酒酵母的顺式作用的详细分析 调控金属硫蛋白基因转录的调控序列 针对铜已经展开了应对。此外，一种反式- 转录诱导所需的作用基因已经被 进行了鉴定和克隆。我们建议对酵母菌的调控 基因是通过积极和消极的相互作用而产生的 各种因素。酵母金属硫蛋白的结构与功能关系 都是通过结合定点突变和 生物物理技术和残基对功能 该蛋白的活性已被鉴定。金属硫蛋白 在更复杂的小鼠细胞中的基因调控也 被分析过了。控制区的系统点突变 揭示了诱导和高效所需的不同残基 抄写。制约这些地区的两个因素是 确认身份并将其分开。