alexa Molecular mechanisms of Nrf2-mediated antioxidant response.
Immunology

Immunology

International Journal of Inflammation, Cancer and Integrative Therapy

Author(s): Li W, Kong AN, Li W, Kong AN

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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. Copyright 2008 Wiley-Liss, Inc.
This article was published in Mol Carcinog and referenced in International Journal of Inflammation, Cancer and Integrative Therapy

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