Keap1 as the redox sensor of the antioxidant response

Arch Biochem Biophys. 2017 Mar 1:617:94-100. doi: 10.1016/j.abb.2016.10.010. Epub 2016 Oct 18.

Abstract

Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant stress is Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1), which is a negative regulator of transcription factor Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and the central hub for sensing endogenous and environmental oxidative and electrophilic stress. In this review, we provide an overview of the mechanisms by which Keap1 orchestrates the antioxidant response and how the system can be targeted for therapy.

Keywords: Electrophile; Nrf2; Reactive oxygen species; Thiol.

Publication types

  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antioxidants / chemistry*
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism*
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Oxidative Stress
  • Phylogeny
  • Reactive Oxygen Species / chemistry
  • Signal Transduction

Substances

  • Antioxidants
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • Oxidants
  • Reactive Oxygen Species