Molecular mechanisms of Nrf2-mediated antioxidant response

Wenge Li, Ah Ng Kong

Research output: Contribution to journalReview article

483 Scopus citations

Abstract

Nrf2 is the key transcription factor regulating the antioxidant response. Nrf2 signaling is repressed by Keap1 at basal condition and induced by oxidative stress. Keap1 is recently identified as a Cullin 3-dependent substrate adaptor protein. A two-sites binding ''hinge & latch'' model vividly depicts how Keap1 can efficiently present Nrf2 as substrate for ubiquitination. Oxidative perturbation can impede Keap1-mediated Nrf2 ubiquitination but fail to disrupt Nrf2/Keap1 binding. Nrf2 per se is a redox-sensitive transcription factor. A new Nrf2-mediated redox signaling model is proposed based on these new discoveries. Free floating Nrf2 protein functions as a redox-sensitive probe. Keap1 instead functions as a gate keeper to control the availability of Nrf2 probes and thus regulates the overall sensitivity of the redox signaling.

Original languageEnglish (US)
Pages (from-to)91-104
Number of pages14
JournalMolecular Carcinogenesis
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

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Keywords

  • Keap1
  • Nrf2
  • Redox

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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