REGULATION OF METALLOTHIONEIN GENES BY HEAVY-METALS APPEARS TO BE MEDIATED BY A ZINC-SENSITIVE INHIBITOR THAT INTERACTS WITH A CONSTITUTIVELY ACTIVE TRANSCRIPTION FACTOR, MTF-1
REGULATION OF METALLOTHIONEIN GENES BY HEAVY-METALS APPEARS TO BE MEDIATED BY A ZINC-SENSITIVE INHIBITOR THAT INTERACTS WITH A CONSTITUTIVELY ACTIVE TRANSCRIPTION FACTOR, MTF-1
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DOI：
10.1073/pnas.91.4.1219
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发表时间：
1994-02-15
影响因子：
11.1
通讯作者：
PALMITER, RD
中科院分区：
文献类型：
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作者：
PALMITER, RD
将具有与可选择报告基因融合的五种金属响应元件的构建体MRE-β Geo转染到BHK细胞中，并分离出可被锌、镉、铋、银、钴、铜、汞或镍诱导高达100倍的稳定克隆。这些金属中的一些，也许是全部，通过取代锌来诱导MRE-β Geo。用编码转录激活因子MTF-1的构建体转染这些细胞导致MRE-β Geo的组成型表达，而在这些细胞中表达反义MTF-1构建体阻止了所有金属的诱导。在没有添加金属的情况下具有高组成型表达的变体细胞系被分离;通过细胞融合恢复正常调节。这些结果表明，金属调节金属硫蛋白基因是由MTF-1与金属反应元件相互作用介导的，锌的功能是从抑制剂中释放MTF-1。
A construct, MRE-beta Geo, with five metal response elements fused fo a selectable reporter gene was transfected into BHK cells and a stable clone that could be induced up to 100-fold by zinc, cadmium, bismuth, silver, cobalt, copper, mercury, or nickle was isolated. Some, and perhaps all, of these metals induce MRE-beta Geo by displacing zinc. Transfection of these cells with a construct encoding the transcriptional activator MTF-1 resulted in constitutive expression of MRE-beta Geo, whereas expression of an antisense MTF-1 construct in these cells prevented induction by all of the metals. A variant cell line with high constitutive expression in the absence of added metals was isolated; normal regulation was restored by cell fusion. These results suggest that regulation of metallothionein genes by metals is mediated by MTF-1 interacting with metal response elements and that zinc functions to release MTF-1 from an inhibitor.