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lüll Molecular mechanisms of Nrf2-mediated antioxidant response Li W; Kong ANMol Carcinog 2009[Feb]; 48 (2): 91-104Nrf2 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.|Animals[MESH]|Antioxidants/*metabolism[MESH]|Humans[MESH]|Intracellular Signaling Peptides and Proteins/metabolism/physiology[MESH]|Kelch-Like ECH-Associated Protein 1[MESH]|NF-E2-Related Factor 2/metabolism/*physiology[MESH]|Oxidative Stress[MESH]|Protein Binding[MESH]|Signal Transduction[MESH] |