Schaffner Georgiev
Fakultäten » Mathematisch-naturwissenschaftliche Fakultät » Molekulare Biologie, Institut für » Transcription and Gene Regulation » Prof. Dr. Walter Schaffner (emeritiert) » Schaffner Georgiev
Completed research project
| Title / Titel | Response of mammalian cells to stress, notably to heavy metal and oxidative stress | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | We are studying the regulation of gene expression (notably that of metallothionein genes) upon exposure of mammalian cells to heavy metals and other stress factors. Metallothioneins (MTs) are small proteins with an extremely high affinity to heavy metals. They function in heavy metal homeostasis, detoxification and radical scavenging; accordingly, transcription of metallothionein genes is induced by heavy metal load. Previously we cloned and characterized the crucial regulatory factor, MTF-1, that binds to metal-responsive promoter elements which confer heavy metal induction to the metallothionein genes. In collaboration with Horst Blüthmann (Basel) and Adriano Aguzzi (Zürich), we have studied the effect of targeted disruption of the MTF-1 regulator gene. Null mutant mouse embryos die from liver decay in utero, with expression of redox-regulating proteins including metallothioneins being impaired. This knockout phenotype is similar to the ones of two other stress regulators, c-Jun and NF-kB p65/relA, which might mean that these factors act in concert to maintain the cellular redox state. We are presently searching for further target genes of MTF-1, and also have developed a cell-free transcription system that depends on MTF-1 and heavy metal (zinc). Furthermore, we have isolated and functionally tested the MTF-1 gene from a fish (Fugu rubripes) and find that heavy metal stress response has been conserved for at least 400 million years. Weitere Informationen |
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| Publications / Publikationen | Günes, C., Heuchel, R., Georgiev, O., Müller, K.-H., Lichtlen, P., Blüthmann, H., Marino, S., Aguzzi, A. and Schaffner, W. (1998). Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. EMBO J.,17(10), 2846-2854.M. Hagmann, R. Bruggmann, L. Xue, O. Georgiev, W. Schaffner, D. Rungger, P. Spaniol and T. Gerster. (1998). Homologous recombination and DNA-end joining reactions in zygotes and early embryos of zebrafish (Danio rerio) and Drosophila melanogaster [see comments]. Biological Chemistry. 6. 673-81.Weitere Informationen | ||||
| Keywords / Suchbegriffe | transcripton, stress, MTF, MT, transcription factor | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Other links to external web pages | http://www.molbio.uzh.ch/groups/schaffner/index.shtml http://www.molbio.uzh.ch/groups/georgiev/index.shtml |
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| Funding source(s) / Unterstützt durch |
Universität Zürich (position pursuing an academic career), SNF (Personen- und Projektförderung) |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 1995 to Dec 2000 |