The "metal transcription factor" MTF-1: biological facts and medical implications

Swiss Med Wkly. 2001 Dec 1;131(45-46):647-52.

Abstract

Metallothioneins (MTs) are a class of small, cysteine-rich proteins that have an important function in heavy metal metabolism and detoxification and in the management of various forms of cell stress. Several lines of evidence suggest a role for metallothioneins in therapy resistance of malignant tumours, regulation of blood pressure and protection against some neurological diseases. Basal and heavy metal-induced expression of the stress-inducible metallothionein-I and -II genes and some other stress-regulated genes depends on the zinc-finger transcription factor MTF-1. MTF-1 acts as a cellular stress-sensor protein and, besides its crucial role in metallothionein expression, is essential for liver development since mice null mutant for MTF-1 die in utero due to hepatocyte degeneration. Under pathological conditions, MTF-1 seems to be involved in clinically important processes such as tumour angiogenesis and drug resistance. It thus seems generally advisable to monitor MTF-1 activity in stress-related processes including aging and carcinogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins
  • Female
  • Humans
  • Male
  • Metallothionein / metabolism*
  • Metallothionein / physiology
  • Metals, Heavy / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Oxidative Stress
  • Pregnancy
  • Pregnancy, Animal
  • Promoter Regions, Genetic
  • Sensitivity and Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology

Substances

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