Mechanistic studies of the Nrf2-Keap1 signaling pathway

Research output: Contribution to journalArticle

677 Scopus citations

Abstract

Since eukaryotic cells constantly encounter various environmental insults, they have evolved defense mechanisms to cope with toxicant- and carcinogen-induced oxidative stress or electrophiles. One of the most important cellular defense mechanisms against oxidative stress or electrophiles is mediated by the transcription factor Nrf2. Under the basal condition, Nrf2-dependent transcription is repressed by a negative regulator Keap1. When cells are exposed to oxidative stress, electrophiles, or chemopreventive agents, Nrf2 escapes Keap1-mediated repression and activates antioxidant responsive element (ARE)-dependent gene expression to maintain cellular redox homeostasis. Beyond its antioxidant function, Nrf2 has recently been recognized as a key factor regulating an array of genes that defend cells against the deleterious effects of environmental insults. Since this Nrf2-dependent cellular defense response is able to protect multi-organs or multi-tissues, activation of Nrf2 has been implicated in conferring protection against many human diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, acute and chronic lung injury, autoimmune diseases, and inflammation. Therefore, understanding of Nrf2 regulation is crucial in the development of drugs for therapeutic intervention. This review will discuss recent progress in the field of the Nrf2-Keap1 signaling pathway, with emphasis on the mechanistic studies of Nrf2 regulation by Keap1, oxidative stress, or chemopreventive compounds.

Original languageEnglish (US)
Pages (from-to)769-789
Number of pages21
JournalDrug Metabolism Reviews
Volume38
Issue number4
DOIs
StatePublished - Jul 1 2006

Keywords

  • Chemopreventive compounds
  • Degradation
  • Keap1
  • Nrf2
  • Oxidative stress
  • Ubiquitin ligase
  • Ubiquitination

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Mechanistic studies of the Nrf2-Keap1 signaling pathway'. Together they form a unique fingerprint.

  • Cite this