Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes

Genes Dev. 2005 Apr 15;19(8):891-6. doi: 10.1101/gad.1301805.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Cation Transport Proteins / metabolism*
  • Cells, Cultured
  • Computational Biology
  • Copper / metabolism*
  • Copper Transporter 1
  • DNA-Binding Proteins
  • Drosophila / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Components
  • Gene Expression Regulation*
  • Green Fluorescent Proteins
  • Ion Transport / physiology
  • Metallothionein / metabolism
  • Protein Binding
  • Transcription Factor MTF-1
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Cation Transport Proteins
  • Copper Transporter 1
  • DNA-Binding Proteins
  • Transcription Factors
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Copper
  • Metallothionein