ArticleMolecular and cellular biology2003
Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 243 citations in OpenAlex.
- DNA recognition, cleavage, and toxic metal ion interaction of an artificial zinc finger protein inside E. coli cells.Protein science : a publication of the Protein Society · 2026Article
- Decreased metallothionein-3 expression in the human spinal cord is a common feature of amyotrophic lateral sclerosis and multiple sclerosis.Scientific reports · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Membrane transporters modulating the toxicity of arsenic, cadmium, and mercury in human cells.Life science alliance · 2025Article
- Deciphering the safeguarding role of cysteine residues in p53 against HCommunications chemistry · 2025Article
- NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.Antioxidants (Basel, Switzerland) · 2024Article
- Engineering a synthetic gene circuit for high-performance inducible expression in mammalian systems.Nature communications · 2024Article
- Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.Acta pharmacologica Sinica · 2024Article
- α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Zinc binding of a Cys2His2-type zinc finger protein is enhanced by the interaction with DNA.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Comparative cisplatin reactivity towards human Zn7-metallothionein-2 and MTF-1 zinc fingers: potential implications in anticancer drug resistance.Metallomics : integrated biometal science · 2022Article
- Is Genetic Engineering a Route to Enhance Microalgae-Mediated Bioremediation of Heavy Metal-Containing Effluents?Molecules (Basel, Switzerland) · 2022Review
- The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1.Nature cell biology · 2022Article
- Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effect of the Forth and Fifth Zinc Finger Deletions of MTF-1 on the Expression of Metal Ion Metabolism Related Gene.Doklady. Biochemistry and biophysics · 2021Article
- The Enigmatic Metallothioneins: A Case of Upward-Looking Research.International journal of molecular sciences · 2021Article
- Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease.Biomedicines · 2021Review
- Soil Saprobic Fungi Differ in Their Response to Gradually and Abruptly Delivered Copper.Frontiers in microbiology · 2020Article
- Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity.The Biochemical journal · 2019Article
- Partial ameliorative effect of Moringa leaf ethanolic extract on the reproductive toxicity and the expression of steroidogenic genes induced by subchronic cadmium in male rats.Environmental science and pollution research international · 2019Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metallothioneins are small, cysteine-rich proteins that avidly bind heavy metals such as zinc, copper, and cadmium to reduce their concentration to a physiological or nontoxic level. Metallothionein gene transcription is induced by several stimuli, notably heavy metal load and oxidative stress. Transcriptional induction of metallothionein genes is mediated by the metal-responsive transcription factor 1 (MTF-1), an essential zinc finger protein that binds to specific DNA motifs termed metal-response elements. In cell-free DNA binding reactions with nuclear extracts, MTF-1 requires elevated zinc concentrations for efficient DNA binding but paradoxically is inactivated by other in vivo inducers such as cadmium, copper, and hydrogen peroxide. Here we have developed a cell-free, MTF-1-dependent transcription system which accurately reproduces the activation of metallothionein gene promoters not only by zinc but also by these other inducers. We found that while transcriptional induction by zinc can be achieved by elevated zinc concentration alone, induction by cadmium, copper, or H2O2 additionally requires the presence of zinc-saturated metallothionein. This is explained by the preferential binding of cadmium or copper to metallothionein or its oxidation by H2O2; the concomitant release of zinc in turn leads to the activation of transcription factor MTF-1. Conversely, thionein, the metal-free form of metallothionein, inhibits activation of MTF-1. The release of zinc from cellular components, including metallothioneins, and the sequestration of zinc by newly produced apometallothionein might be a basic mechanism to regulate MTF-1 activity upon cellular stress.
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