Gralla E B, Thiele D J, Silar P, Valentine J S
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024-1569.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8558-62. doi: 10.1073/pnas.88.19.8558.
Copper, zinc superoxide dismutase (SOD1 gene product) (superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a copper-containing enzyme that functions to prevent oxygen toxicity. In the yeast Saccharomyces cerevisiae, copper levels exert some control over the level of SOD1 expression. We show that the ACE1 transcriptional activator protein, which is responsible for the induction of yeast metallothionein (CUP1) in response to copper, also controls the SOD1 response to copper. A single binding site for ACE1 is present in the SOD1 promoter region, as demonstrated by DNase I protection and methylation interference experiments, and is highly homologous to a high-affinity ACE1 binding site in the CUP1 promoter. The functional importance of this DNA-protein interaction is demonstrated by the facts that (i) copper induction of SOD1 mRNA does not occur in a strain lacking ACE1 and (ii) it does not occur in a strain containing a genetically engineered SOD1 promoter that lacks a functional ACE1 binding site.
铜锌超氧化物歧化酶（SOD1基因产物）（超氧化物：超氧化物氧化还原酶，EC 1.15.1.1）是一种含铜酶，其功能是防止氧中毒。在酿酒酵母中，铜水平对SOD1表达水平有一定控制作用。我们发现，负责响应铜诱导酵母金属硫蛋白（CUP1）的ACE1转录激活蛋白，也控制SOD1对铜的响应。如DNA酶I保护和甲基化干扰实验所示，SOD1启动子区域存在一个ACE1结合位点，且与CUP1启动子中的高亲和力ACE1结合位点高度同源。这种DNA-蛋白质相互作用的功能重要性体现在以下事实：（i）在缺乏ACEI的菌株中，铜不会诱导SOD1 mRNA的产生；（ii）在含有缺乏功能性ACE1结合位点的基因工程SOD1启动子的菌株中，铜也不会诱导SOD1 mRNA的产生。
