title: Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes.
abstract: From insects to mammals, metallothionein genes are induced in response to heavy metal load by the transcription factor MTF-1, which binds to short DNA sequence motifs, termed metal response elements (MREs). Here we describe a novel and seemingly paradoxical role for MTF-1 in Drosophila in that it also mediates transcriptional activation of Ctr1B, a copper importer, upon copper depletion. Activation depends on the same type of MRE motifs in the upstream region of the Ctr1B gene as are normally required for metal induction. Thus, a single transcription factor, MTF-1, plays a direct role in both copper detoxification and acquisition by inducing the expression of metallothioneins and of a copper importer, respectively.
authors.affiliation: Institute of Molecular Biology, University of Zurich, CH-8057, Zurich, Switzerland.
authors.forename: Anand
authors.initials: A
authors.lastname: Selvaraj
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Balamurugan
authors.forename: Hasmik
authors.initials: H
authors.lastname: Yepiskoposyan
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019295:Computational Biology; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D040461:Gene Components; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D017136:Ion Transport / Q000502:physiology; D008668:Metallothionein / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000097809:Transcription Factor MTF-1
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000079923:Copper Transporter 1; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D008668:Metallothionein; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1; C485184:enhanced green fluorescent protein