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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison

K. Balamurugan / D. Egli / A. Selvaraj / B. Zhang / O. Georgiev / W. Schaffner

Citation Information: Biological Chemistry. Volume 385, Issue 7, Pages 597–603, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2004.074, June 2005

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The zinc finger transcription factor MTF-1 (metalresponsive transcription factor-1) is conserved from insects to vertebrates. Its major role in both organisms is to control the transcription of genes involved in the homeostasis and detoxification of heavy metal ions such as Cu[2+], Zn[2+] and Cd [2+]. In mammals, MTF-1 serves at least two additional roles. First, targeted disruption of the MTF-1 gene results in death at embryonic day 14 due to liver degeneration, revealing a stagespecific developmental role. Second, under hypoxicanoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PlGF), an angiogenic protein. Recently we characterized dMTF-1, the Drosophila homolog of mammalian MTF-1. Here we present a series of studies to compare the metal response in mammals and insects, which reveal common features but also differences. A human MTF-1 transgene can restore to a large extent metal tolerance to flies lacking their own MTF-1 gene, both at low and high copper concentrations. Likewise, Drosophila MTF-1 can substitute for human MTF-1 in mammalian cell culture, although both the basal and the metalinduced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothioneintype promoters respond poorly, if at all, to Hg[2+] in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.

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