共 39 条
Cadmium-mediated activation of the metal response element in human neuroblastoma cells lacking functional metal response element-binding transcription factor-1
被引:26
作者:
Chu, WA
Moehlenkamp, JD
Bittel, D
Andrews, GK
Johnson, JA
机构:
[1] Univ Kansas, Med Ctr, Dept Pharmacol, Kansas City, KS 66160 USA
[2] Univ Kansas, Med Ctr, Dept Toxicol, Kansas City, KS 66160 USA
[3] Univ Kansas, Med Ctr, Dept Therapeut, Kansas City, KS 66160 USA
[4] Univ Kansas, Med Ctr, Dept Biochem, Kansas City, KS 66160 USA
[5] Univ Kansas, Med Ctr, Dept Mol Biol, Kansas City, KS 66160 USA
关键词:
D O I:
10.1074/jbc.274.9.5279
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Metal response element-binding transcription factor-1 (MTF-1) binds specifically to metal response elements (MREs) and transactivates metallothionein (MT) gene expression in response to zinc and cadmium. This investigation contrasts the mechanism of mouse MT gene (mMT I) promoter activation by cadmium and zinc in IMR-32 human neuroblastoma cells to determine whether MTF-1 binding to the MRE is necessary for activation by these metals. Cadmium activated a mMT-1 promoter (-150 base pairs) luciferase reporter 20-25-fold through a MRE-dependent mechanism. In contrast, zinc had little effect on the mMT-1 luciferase reporter, IMR-32 cells lacked MRE binding activity, and treatment with zinc in vitro or in vivo did not generate a MTF-1 MRE complex, suggesting that IMR-32 cells lack functional MTF-1 Overexpression of mMTF-1 regenerated a zinc-mediated induction of the MRE without affecting cadmium activation. Because no other transition metals tested activated the MRE, this effect appeared to be cadmium-specific. These data demonstrate that in IMR-32 human neuroblastoma cells, zinc and cadmium can use independent mechanisms for activation of the mMT-I promoter and cadmium-mediated MRE activation is independent of TTF-l and zinc.
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页码:5279 / 5284
页数:6
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