Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1)

Arch Biochem Biophys. 2007 Jul 15;463(2):201-10. doi: 10.1016/j.abb.2007.03.019. Epub 2007 Apr 4.

Abstract

The regulation of divalent zinc has been observed in a wide range of organisms. Since this metal is an essential nutrient, but also toxic in excess, zinc homeostasis is crucial for normal cellular functioning. The metal-responsive-element-binding transcription factor-1 (MTF-1) is a key regulator of zinc in higher eukaryotes ranging from insects to mammals. MTF-1 controls the expression of metallothioneins (MTs) and a number of other genes directly involved in the intracellular sequestration and transport of zinc. Although the diverse functions of MTF-1 extend well beyond zinc homeostasis to include stress-responses to heavy metal toxicity, oxidative stress, and selected chemical agents, in this review we focus on the recent advances in understanding the mechanisms whereby MTF-1 regulates MT gene expression to protect the cell from fluctuations in environmental zinc. Particular emphasis is devoted to recent studies involving the Cys2His2 zinc finger DNA-binding domain of MTF-1, which is an important contributor to the zinc-sensing and metal-dependent transcriptional activation functions of this protein.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Metallothionein / metabolism
  • Metallothionein / physiology
  • Mice
  • Molecular Sequence Data
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Zinc / metabolism*
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • transcription factor MTF-1
  • Metallothionein
  • Zinc