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

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.

► MTF-1 activates target gene expression in response to heavy metals.
► Oxidative stress and hypoxia can also induce MTF-1 dependent gene expression.
► MTF-1 is conserved from insects to mammals.
► Drosophila and mammalian MTF-1 share several key functions.
► Nevertheless, there is little sequence similarity outside of the zinc finger domain.