Differential control of the metal-mediated activation of the human heme oxygenase-1 and metallothionein IIA genes.

Differential control of the metal-mediated activation of the human heme oxygenase-1 and metallothionein IIA genes.
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金属介导的人血红素加氧酶-1 和金属硫蛋白 IIA 基因激活的差异控制。

DOI:
10.1006/bbrc.1995.1167
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发表时间:
1995
影响因子:
3.1
通讯作者:
Shigeki Shibahara
Shigeki Shibahara
中科院分区:
生物学4区
文献类型:
--
作者:
K. Takeda;Hideaki Fujita;Shigeki Shibahara

文献摘要

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镉或锌可显著诱导HeLa细胞中的血红素加氧酶-1和金属硫蛋白IIA,前者是血红素分解代谢的关键酶,后者是一种带有半胱氨酸簇的小分子金属结合蛋白。这两种蛋白质都被认为参与了抵御金属毒性的防御系统。在这里,我们通过瞬时表达分析表明,人血红素加氧酶-1基因的镉反应元件(CDRE)对锌不反应,而人金属硫蛋白IIA基因的金属调节元件(MRE)能够对镉或锌反应。CDRE被特定的核蛋白(S)识别,但不能与金属硫蛋白IIA基因的MRE结合。这些结果表明,每个基因启动子的金属选择性激活是由不同的机制介导的。
Heme oxygenase-1, an essential enzyme in heme catabolism, and metallothionein IIA, a small metal-binding protein with clusters of cysteins, are remarkably induced in HeLa cells following the treatment with cadmium or zinc. Both proteins are considered to be involved in the defense system against metal toxicity. Here we showed by transient expression assays that the cadmium-responsive element (CdRE) of the human heme oxygenase-1 gene is not responsive to zinc, whereas a metal-regulatory element (MRE) of the human metallothionein IIA gene is able to respond to either cadmium or zinc. The CdRE is recognized by a certain nuclear protein(s) which is however unable to bind to an MRE of the metallothionein IIA gene. These results suggest that the metal-selective activation of each gene promoter is mediated by a separate mechanism.