title: Molecular mechanisms of Nrf2-mediated antioxidant response.
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.
authors.affiliation: Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Wenge
authors.initials: W
authors.lastname: Li
authors.forename: Ah-Ng
authors.initials: AN
authors.lastname: Kong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human