The taste of heavy metals: gene regulation by MTF-1

Biochim Biophys Acta. 2012 Sep;1823(9):1416-25. doi: 10.1016/j.bbamcr.2012.01.005. Epub 2012 Jan 20.


The metal-responsive transcription factor-1 (MTF-1, also termed MRE-binding transcription factor-1 or metal regulatory transcription factor-1) is a pluripotent transcriptional regulator involved in cellular adaptation to various stress conditions, primarily exposure to heavy metals but also to hypoxia or oxidative stress. MTF-1 is evolutionarily conserved from insects to humans and is the main activator of metallothionein genes, which encode small cysteine-rich proteins that can scavenge toxic heavy metals and free radicals. MTF-1 has been suggested to act as an intracellular metal sensor but evidence for direct metal sensing was scarce. Here we review recent advances in our understanding of MTF-1 regulation with a focus on the mechanism underlying heavy metal responsiveness and transcriptional activation mediated by mammalian or Drosophila MTF-1. This article is part of a Special Issue entitled: Cell Biology of Metals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Homeostasis / physiology
  • Humans
  • Hypoxia / metabolism
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Metals, Heavy / metabolism*
  • Metals, Heavy / toxicity
  • Molecular Sequence Data
  • Oxidative Stress
  • Protein Structure, Tertiary
  • Signal Transduction / drug effects
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / drug effects*


  • DNA-Binding Proteins
  • Metals, Heavy
  • Transcription Factors
  • transcription factor MTF-1
  • Metallothionein