Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy metals

Otsuka, Fuminori; Okugaito, Izumi; Ohsawa, Motoyasu; Iwamatsu, Akihiro; Suzuki, Kaoru; Koizumi, Satoshi

doi:10.1016/s0167-4781(00)00110-x

Cited by 39 publications

(31 citation statements)

References 27 publications

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“…Subsequently the mouse gene was cloned and characterized as a ubiquitously expressed zinc finger transcription factor essential for basal and heavy metal-induced expression of metallothioneins [22,23]. The cloning of MTF-1 genes of human, fish and Drosophila followed [24][25][26][27]. MTF-1 null mutant mouse embryos develop severe liver degeneration and die in utero at approximately day 14 of gestation [28].…”

Section: Introductionmentioning

confidence: 99%

Characterization of MtnE, the fifth metallothionein member in Drosophila

et al. 2011

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Metallothioneins (MTs) constitute a family of cysteine-rich, low molecular weight metal-binding proteins which occur in almost all forms of life. They bind physiological metals, such as zinc and copper, as well as nonessential, toxic heavy metals, such as cadmium, mercury, and silver. MT expression is regulated at the transcriptional level by metal-regulatory transcription factor 1 (MTF-1), which binds to the metal-response elements (MREs) in the enhancer/promoter regions of MT genes. Drosophila was thought to have four MT genes, namely, MtnA, MtnB, MtnC, and MtnD. Here we characterize a new fifth member of Drosophila MT gene family, coding for metallothionein E (MtnE). The MtnE transcription unit is located head-to-head with the one of MtnD. The intervening sequence contains four MREs which bind, with different affinities, to MTF-1. Both of the divergently transcribed MT genes are completely dependent on MTF-1, whereby MtnE is consistently more strongly transcribed. MtnE expression is induced in response to heavy metals, notably copper, mercury, and silver, and is upregulated in a genetic background where the other four MTs are missing.

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Section: Introductionmentioning

confidence: 99%

Characterization of MtnE, the fifth metallothionein member in Drosophila

et al. 2011

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“…The MTF-1 binds to the MRE (metal response element) sequence within the MT gene promoter. Binding of MTF-1 to MRE initiates the process of MT gene transcription (Langmade et al, 2000;Otsuka et al, 2000;Saydam et al, 2002). The remaining metals (e.g.…”

Section: Mt Structure and Synthesismentioning

confidence: 99%

Expression of Metallothionein in Oral Cancer

Dzięgiel¹,

Puła²,

Podhorska-Okołów³

2012

Oral Cancer

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“…18,19) Zinc regulatory factor (ZRF) was also isolated from HeLa cell nuclear extract as an MRE-binding transcriptional factor (MREBT) by Otsuka et al 20) The amino acid sequence of ZRF is almost identical to human MTF-1 (hMTF-1) with only one difference at amino acid 185 in the second zinc finger domain [histidine (CAC) in hMTF-1 and tyrosine (TAC) in ZRF]. 21) Koizumi et al 22) reported that a reporter gene expression, which was driven by MREs, was induced by zinc in the hMTF-1 overexpressing cells, but not in the ZRF overexpressing cells, although basal levels of reporter gene expression were significantly elevated by overexpression of each in both variants. The single amino acid difference between these two MREBT variants may influence MT gene expression and the extent of manifestation of cadmium toxicity in humans.…”

Section: Introductionmentioning

confidence: 99%

Original MRE-binding Transcriptional Factor Gene in Normal Humans is ZRF, not MTF-1.

Kita

Miura

Yoshida

et al. 2001

JOURNAL OF HEALTH SCIENCE

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Metallothionein gene is transcriptionally regulated by heavy metals through cis-acting metal responsive elements (MREs). Two proteins, metal-regulatory transcription factor-1 (MTF-1) and zinc regulatory factor (ZRF), have been isolated and cloned from human cells as MRE-binding transcriptional factor (MREBT). These proteins are almost identical to each other, except for only one base substitution at codon 185 that causes an amino acid change from histidine to tyrosine. This single amino acid difference has been reported to influence zinc-responsive transcriptional activities. In this study, we determined the nucleotide sequence of the region containing codon 185 in DNA samples obtained from normal Japanese (n = 30) and three human-derived cultured cell lines. The findings indicate that all subjects have the same sequence identical to ZRF, suggesting that ZRF is the original MREBT gene in normal humans, and MTF-1 is its minor variant.

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Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy metals

Cited by 39 publications

References 27 publications

Characterization of MtnE, the fifth metallothionein member in Drosophila

Characterization of MtnE, the fifth metallothionein member in Drosophila

Expression of Metallothionein in Oral Cancer

Original MRE-binding Transcriptional Factor Gene in Normal Humans is ZRF, not MTF-1.

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