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Title: Molecular mechanisms of Nrf2-mediated antioxidant response.

Authors: Li, Wenge; Kong, Ah-Ng

Published In Mol Carcinog, (2009 Feb)

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.

PubMed ID: 18618599 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/metabolism*; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Intracellular Signaling Peptides and Proteins/physiology; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2/metabolism; NF-E2-Related Factor 2/physiology*; Oxidative Stress; Protein Binding; Signal Transduction

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