Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison.
The zinc finger transcription factor MTF-1 (metal-responsive 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 Cu2+, Zn2+ and Cd2+. 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 stage-specific developmental role. Second, under hypoxic-anoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PIGF), 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 metal-induced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothionein-type promoters respond poorly, if at all, to Hg2+ in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Kuppusamy
K
Balamurugan
Dieter
D
Egli
Anand
A
Selvaraj
Bo
B
Zhang
Oleg
O
Georgiev
Walter
W
Schaffner
D000818:Animals; D003300:Copper / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004330:Drosophila; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D008628:Mercury / Q000494:pharmacology; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics; D019216:Metals, Heavy / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015032:Zinc / Q000494:pharmacology; D000097809:Transcription Factor MTF-1
D003300:Copper; D004268:DNA-Binding Proteins; D008628:Mercury; D008668:Metallothionein; D019216:Metals, Heavy; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1