Oleg Georgiev
(Oberassistent, Prof. Schaffner)
Institut für Molekularbiologie
Universität Zürich
Winterthurerstrasse 190
8057 Zürich
Schweiz
+41 44 63 53177
Group members
Research
Role of the Transcription Factor MTF-1 in Cellular Stress Response.
Abstract
Our research efforts concern the analysis of cellular stress response at the level of transcription. One of the key factors in the response to heavy metals (and oxidative stress) is MTF-1, a zinc finger transcription factor that binds to so-called MRE sequences. MREs (core sequence: TGCRCNC) are found in the promoters of a number of stress associated genes, including those encoding metallothioneins, gamma-glutamyl cysteine synthase, lipocalins, Znt-1, G6PD. Targeted disruption of the MTF-1 gene results in liver degeneration and embryonic lethality. The distribution, mechanism of activation, and evolutionary conservation of MTF-1 are under investigation. Towards the latter goal, the MTF-1 genes of the mouse, the pufferfish (Fugu rubripes) and the fruit fly Drosophila have recently been sequenced and functionally characterized.
Recent publications
Chen X, Hua H, Balamurugan K, Kong X, Zhang L, George GN, Georgiev O, Schaffner W and Giedroc DP (2008) "Copper sensing function of Drosophila metal-responsive transcription factor-1 is mediated by a tetranuclear Cu(I) cluster." Nucleic Acids Res 36(9): 3128-3138. Abstract
Balamurugan K, Egli D, Hua H, Rajaram R, Seisenbacher G, Georgiev O and Schaffner W (2007) "Copper homeostasis in Drosophila by complex interplay of import, storage and behavioral avoidance." Embo J 26(4): 1035-1044. Abstract
Milev S, Bjelic S, Georgiev O and Jelesarov I (2007) "Energetics of peptide recognition by the second PDZ domain of human protein tyrosine phosphatase 1E." Biochemistry 46(4): 1064-1078. Abstract
Paumi CM, Menendez J, Arnoldo A, Engels K, Iyer KR, Thaminy S, Georgiev O, Barral Y, Michaelis S and Stagljar I (2007) "Mapping protein-protein interactions for the yeast ABC transporter Ycf1p by integrated split-ubiquitin membrane yeast two-hybrid analysis." Mol Cell 26(1): 15-25. Abstract
Takeuchi H, Georgiev O, Fetchko M, Kappeler M, Schaffner W and Egli D (2007) "In vivo construction of transgenes in Drosophila." Genetics 175(4): 2019-2028. Abstract
Egli D, Domenech J, Selvaraj A, Balamurugan K, Hua H, Capdevila M, Georgiev O, Schaffner W and Atrian S (2006) "The four members of the Drosophila metallothionein family exhibit distinct yet overlapping roles in heavy metal homeostasis and detoxification." Genes Cells 11(6): 647-658. Abstract
Egli D, Yepiskoposyan H, Selvaraj A, Balamurugan K, Rajaram R, Simons A, Multhaup G, Mettler S, Vardanyan A, Georgiev O and Schaffner W (2006) "A family knockout of all four Drosophila metallothioneins reveals a central role in copper homeostasis and detoxification." Mol Cell Biol 26(6): 2286-2296. Abstract
Yepiskoposyan H, Egli D, Fergestad T, Selvaraj A, Treiber C, Multhaup G, Georgiev O and Schaffner W (2006) "Transcriptome response to heavy metal stress in Drosophila reveals a new zinc transporter that confers resistance to zinc." Nucleic Acids Res 34(17): 4866-4877. Abstract
Selvaraj A, Balamurugan K, Yepiskoposyan H, Zhou H, Egli D, Georgiev O, Thiele DJ and Schaffner W (2005) "Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes." Genes Dev 19(8): 891-896. Abstract
Cramer M, Nagy I, Murphy BJ, Gassmann M, Hottiger MO, Georgiev O and Schaffner W (2005) "NF-kappaB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells." Biol Chem 386(9): 865-872. Abstract
Wimmer U, Wang Y, Georgiev O and Schaffner W (2005) "Two major branches of anti-cadmium defense in the mouse: MTF-1/metallothioneins and glutathione." Nucleic Acids Res 33(18): 5715-5727. Abstract
Hafliger P, Agorastos N, Spingler B, Georgiev O, Viola G and Alberto R (2005) "Induction of DNA-Double-Strand Breaks by Auger Electrons from (99m)Tc Complexes with DNA-Binding Ligands." Chembiochem 6(2): 414-421. Abstract
Balamurugan K, Egli D, Selvaraj A, Zhang B, Georgiev O and Schaffner W (2004) "Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison." Biol Chem 385(7): 597-603. Abstract
Sturzenbaum SR, Georgiev O, Morgan AJ and Kille P (2004) "Cadmium detoxification in earthworms: from genes to cells." Environ Sci Technol 38(23): 6283-6289. Abstract
Wang Y, Lorenzi I, Georgiev O and Schaffner W (2004) "Metal-responsive transcription factor-1 (MTF-1) selects different types of metal response elements at low vs. high zinc concentration." Biol Chem 385(7): 623-632. Abstract
Wang Y, Wimmer U, Lichtlen P, Inderbitzin D, Stieger B, Meier PJ, Hunziker L, Stallmach T, Forrer R, Rulicke T, Georgiev O and Schaffner W (2004) "Metal-responsive transcription factor-1 (MTF-1) is essential for embryonic liver development and heavy metal detoxification in the adult liver." Faseb J 18(10): 1071-1079. Abstract
Valkova C, Georgiev O, Karagyozov L and Milchev G (2003) "Silencing of retroviral vector transduced LacZ reporter gene by frameshift mutation." Biotechnol Bioeng 84(1): 1-6. Abstract
Grozdanov P, Georgiev O and Karagyozov L (2003) "Complete sequence of the 45-kb mouse ribosomal DNA repeat: analysis of the intergenic spacer." Genomics 82(6): 637-643. Abstract
Zhang B, Georgiev O, Hagmann M, Gunes C, Cramer M, Faller P, Vasak M and Schaffner W (2003) "Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein." Mol Cell Biol 23(23): 8471-8485. Abstract
Saydam N, Steiner F, Georgiev O and Schaffner W (2003) "Heat and heavy metal stress synergize to mediate transcriptional hyperactivation by metal-responsive transcription factor MTF-1." J Biol Chem 278(34): 31879-31883. Abstract
Egli D, Selvaraj A, Yepiskoposyan H, Zhang B, Hafen E, Georgiev O and Schaffner W (2003) "Knockout of 'metal-responsive transcription factor' MTF-1 in Drosophila by homologous recombination reveals its central role in heavy metal homeostasis." Embo J 22(1):100-108 Abstract
Saydam N, Georgiev O, Nakano MY, Greber UF and Schaffner W (2001) "Nucleo-cytoplasmic trafficking of metal-regulatory transcription factor 1 is regulated by diverse stress signals." J Biol Chem 276(27):25487-25495 Abstract
Zhang B, Egli D, Georgiev O and Schaffner W (2001) "The Drosophila homolog of mammalian zinc finger factor MTF-1 activates transcription in response to heavy metals." Mol Cell Biol 21(14):4505-4514 Abstract
Lichtlen P, Wang Y, Belser T, Georgiev O, Certa U, Sack R and Schaffner W (2001) "Target gene search for the metal-responsive transcription factor MTF-1." Nucleic Acids Res 29(7):1514-1523 Abstract
Auf der Maur, A., Belser, T.,Wang, Y., Günes, C., Lichtlen, P., Georgiev, O., and Schaffner, W. (2000). Characterization of the mouse gene for the heavy metal-responsive transcription factor MTF-1. Cell Stress & Chaperones 5, 196-206. Abstract
Schneider, S., Buchert, M., Georgiev, O., Catimel, B., Halford, M., Stacker, S.A., Baechi, T., Moelling, K., and Hovens, C.M. (1999). Mutagenesis and selection of PDZ domains that bind new protein targets. Nature Biotechnology 17, 170-175. Abstract
Lichtlen, P., Georgiev, O., Schaffner, W., Aguzzi, A., and Brandner, S. (1999). The heavy metal-responsive transcription factor–1 (MTF–1) is not required for neural differentiation. Biol.Chem. 380, 711-715. Abstract
Auf der Maur, A., Belser, T., Elgar, G., Georgiev, O. and Schaffner, W.(1999). Characterization of the transcription factor MTF–1 from the Japanese pufferfish (Fugu rubripes) reveals evolutionary conservation of heavy metal stress response. Biol. Chem. 380, 175-185. Abstract
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. Abstract
Hagmann, M., Bruggmann, R., Xue, L., Georgiev, O., Schaffner, W., Rungger, D., Spaniol, P., and Gerster, T. (1998). Homologous recombination and DNA-end joining reactions in zygotes and early embryos of zebrafish (Danio rerio) and Drosophila melanogaster [see comments]. Biological Chemistry. 379. 673-681. Abstract
Moosmann, P., Georgiev, O., Thiesen, H.J., Hagmann, M., and Schaffner, W. (1997). Silencing of RNA polymerases II and III-dependent transcription by the KRAB protein domain of KOX1, a Kruppel-type zinc finger factor. Biological Chemistry 378(7):669-677.
Bourquin, J.P., Stagljar, I., Meier, P., Moosmann, P., Silke, J., Baechi, T., Georgiev, O., and Schaffner, W. (1997). A serine/arginine-rich nuclear matrix cyclophilin interacts with the C-terminal domain of RNA polymerase II. Nucleic Acids Research 25(11):2055-2061.
Tanner, S., Stagljar, I., Georgiev, O., Schaffner, W., and Bourquin, J.P. (1997). A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain. Biological Chemistry 378(6):565-571.
Hagmann, M., Georgiev, O., and Schaffner, W. (1997). The VP16 paradox: herpes simplex virus VP16 contains a long-range activation domain but within the natural multiprotein complex activates only from promoter-proximal positions. Journal of Virology 71(8):5952-5962.
Radtke, F., Hug, M., Georgiev, O., Matsuo, K., and Schaffner, W. (1996). Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites. Biological Chemistry 377(1):47-56.
Moosmann, P., Georgiev, O., Le Douarin, B., Bourquin, J.P., and Schaffner, W.(1996). Transcriptional repression by RING finger protein TIF1 beta that interacts with the KRAB repressor domain of KOX1. Nucleic Acids Research 24(24):4859-4867.
Gstaiger, M., Hovens, C., Georgiev, O., Knoepfel, L., and Schaffner, W. (1996). BZLF1 (ZEBRA, Zta) protein of Epstein-Barr virus selected in a yeast one-hybrid system by binding to a consensus site in the IgH intronic enhancer: a role in immunoglobulin expression?. Biological Chemistry 377(10):669-673.
Hagmann, M., Adlkofer, K., Pfeiffer, P., Bruggmann, R., Georgiev, O., Rungger, D., and Schaffner W. (1996). Dramatic changes in the ratio of homologous recombination to nonhomologous DNA-end joining in oocytes and early embryos of Xenopus laevis. Biological Chemistry 377(4):239-250.
Gstaiger, M., Georgiev, O., and Schaffner, W. (1996). Fine mapping of protein interaction surfaces with a PCR-based mutagenesis screen in yeast. Trends in Genetics 12(10):393-394.
Knoepfel, L., Georgiev, O., Nielsen, P., and Schaffner, W. (1996). Cloning and characterization of the murine B-cell specific transcriptional coactivator Bob1. Biological Chemistry 377(2):139-145
Georgiev, O., Bourquin, J.P., Gstaiger, M., Knoepfel, L., Schaffner, W., and Hovens, C. (1996). Two versatile eukaryotic vectors permitting epitope tagging, radiolabelling and nuclear localisation of expressed proteins. Gene 168(2):165-167.
Gstaiger, M., Georgiev, O., van Leeuwen, H., van der Vliet, P., and Schaffner, W. (1996). The B cell coactivator Bob1 shows DNA sequence-dependent complex formation with Oct-1/Oct-2 factors, leading to differential promoter activation. EMBO Journal 15(11):2781-2790.
Hug, M., Silke, J., Georgiev, O., Rusconi, S., Schaffner, W., and Matsuo, K. (1996). Transcriptional repression by methylation: cooperativity between a CpG cluster in the promoter and remote CpG-rich regions. FEBS Letters 379(3):251-254.
