Mammalian metal response element-binding transcription factor-1 functions as a zinc sensor in yeast, but not as a sensor of cadmium or oxidative stress.

Mammalian metal response element-binding transcription factor-1 functions as a zinc sensor in yeast, but not as a sensor of cadmium or oxidative stress.
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哺乳动物金属反应元件结合转录因子-1 在酵母中充当锌传感器,但不充当镉或氧化应激的传感器。

DOI:
10.1093/nar/gkf432
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发表时间:
2002
影响因子:
14.9
通讯作者:
Andrews,GlenK
Andrews,GlenK
中科院分区:
生物学2区
文献类型:
--
作者:
Daniels,PatrickJ;Bittel,Doug;Smirnova,IrinaV;Winge,DennisR;Andrews,GlenK

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锌指蛋白,金属反应元件结合转录因子-1(MTF-1)调节基因的表达以响应金属离子和氧化应激。发生这种情况的确切机制尚不清楚。为了进一步研究这个问题,小鼠MTF-1在酵母中表达,并测试激活金属反应元件驱动的报告基因表达的能力。锌是报告基因表达的有效诱导剂。一般来说,锌诱导的大小取决于培养基中锌的浓度,但与MTF-1表达的量无关。锌诱导也发生在含有天然小鼠金属硫蛋白-I近端启动子的整合或附加型报告质粒中。MTF-1的指5和6以锌依赖性方式在体外稳定蛋白质的DNA结合活性,其缺失并没有减少锌对附加型或整合型启动子的诱导。然而,Gal 4 DNA结合结构域- MTF-1融合蛋白,其与Gal 4响应启动子组成性结合,不是锌诱导的,而是引起报告基因表达的组成性激活。这表明锌激活MTF-1的DNA结合活性是其在酵母中金属调节功能的限速步骤。相比之下,MTF-1对镉或过氧化氢没有反应,这表明在酵母中未发现的不同的共激活剂或信号转导级联需要通过这种有毒金属和氧化应激介导MTF-1激活基因表达。
The zinc finger protein, metal response element‐binding transcription factor‐1 (MTF‐1) regulates the expression of genes in response to metal ions and oxidative stress. The precise mechanisms by which this occurs are not understood. To further examine this problem, mouse MTF‐1 was expressed inSaccharomyces cerevisiaeand tested for the ability to activate metal response element‐driven reporter gene expression. Zinc was an effective inducer of reporter gene expression. In general, the magnitude of zinc induction was dependent on the concentration of zinc in the culture medium, but independent of the amount of MTF‐1 expression. Zinc induction also occurred with either integrated or episomal reporter plasmids containing the native mouse metallothionein‐I proximal promoter. Deletion of fingers 5 and 6 of MTF‐1, which function in a zinc‐dependent manner to stabilize the DNA‐binding activity of the proteinin vitro, did not diminish the zinc induction of either episomal or integrated promoters. However, a Gal4 DNA‐binding domain– MTF‐1 fusion protein, which binds constitutively to the Gal4‐responsive promoter, was not zinc inducible but caused constitutive activation of reporter gene expression. This suggests that zinc activation of the DNA‐binding activity of MTF‐1 is the rate limiting step in its metalloregulatory function in yeast. In contrast, MTF‐1 was not responsive to either cadmium or hydrogen peroxide, suggesting that distinct co‐activators or signal transduction cascades not found in yeast are required to mediate MTF‐1 activation of gene expression by this toxic metal and by oxidative stress.
DOI: 10.1021/bi0112208
发表时间: 2001-12-18
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
Apuy, JL;Chen, XH;Giedroc, DP
通讯作者: Giedroc, DP
DOI: 10.1021/bi9913000
发表时间: 1999-09-28
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
Chen, XH;Chu, MH;Giedroc, DP
通讯作者: Giedroc, DP
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DOI: 10.1242/dev.100.3.463
发表时间: 1987
期刊: Development (Cambridge, England)
影响因子: --
作者:
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来自面包酵母的结晶醇脱氢酶。
DOI: 10.1016/s0021-9258(19)51151-6
发表时间: 1950
期刊: The Journal of biological chemistry
影响因子: --
作者:
E. Racker
通讯作者: E. Racker