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血管紧张素转换酶2(ACE2),一种与SWI5同源的酵母金属硫蛋白表达激活剂。

ACE2, an activator of yeast metallothionein expression which is homologous to SWI5.

作者信息

Butler G, Thiele D J

机构信息

Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.

出版信息

Mol Cell Biol. 1991 Jan;11(1):476-85. doi: 10.1128/mcb.11.1.476-485.1991.

Abstract

Transcription of the Saccharomyces cerevisiae metallothionein gene CUP1 is induced in response to high environmental levels of copper. Induction requires the ACE1 gene product, which binds to specific sites in the promoter region of the CUP1 gene. In this study, we found that deleting the entire coding sequence of the ACE1 gene resulted in a decrease in basal-level transcription of CUP1 to low but detectable levels and conferred a copper-sensitive phenotype to the cells. We have isolated a gene, designated ACE2, which when present on a high-copy-number plasmid suppresses the copper-sensitive phenotype of an ace1-deletion strain. The presence of multiple copies of the ACE2 gene enhanced expression of an unlinked CUP1-lacZ fusion integrated in the yeast genome and resulted in an increase in the steady-state levels of CUP1 mRNA in an ace1-deletion background. A large deletion of the coding region of the genomic copy of ACE2 resulted in a decrease in steady-state levels of CUP1 mRNA, indicating that ACE2 plays a role in regulating basal-level expression of CUP1. The ACE2 open reading frame encodes a polypeptide of 770 amino acids, with putative zinc finger structures near the carboxyl terminus. This protein is 37% identical to the SWI5 gene product, an activator of HO gene transcription in S. cerevisiae, suggesting that ACE2 and SWI5 may have functional similarities.

摘要

酿酒酵母金属硫蛋白基因CUP1的转录是在环境中铜含量高时被诱导的。诱导需要ACE1基因产物,它能与CUP1基因启动子区域的特定位点结合。在本研究中,我们发现删除ACE1基因的整个编码序列会导致CUP1的基础水平转录下降到低但可检测的水平,并赋予细胞铜敏感表型。我们分离出了一个名为ACE2的基因,当它存在于高拷贝数质粒上时,能抑制ace1缺失菌株的铜敏感表型。ACE2基因的多个拷贝的存在增强了整合在酵母基因组中的非连锁CUP1-lacZ融合基因的表达,并导致ace1缺失背景下CUP1 mRNA的稳态水平增加。ACE2基因组拷贝编码区的大片段缺失导致CUP1 mRNA的稳态水平下降,表明ACE2在调节CUP1的基础水平表达中起作用。ACE2开放阅读框编码一个770个氨基酸的多肽,在羧基末端附近有假定的锌指结构。该蛋白与酿酒酵母中HO基因转录激活因子SWI5基因产物有37%的同一性,这表明ACE2和SWI5可能具有功能相似性。

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