title: Nrf2-Keap1 defines a physiologically important stress response mechanism.
abstract: The transcription factor Nrf2 regulates the basal and inducible expression of numerous detoxifying and antioxidant genes. The cytoplasmic protein Keap1 interacts with Nrf2 and represses its function. Analysis of keap1-knockout mice provides solid evidence that Keap1 acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses. The simultaneous ablation of the keap1 and nrf2 genes reversed all apparent phenotypes of the Keap1-deficient mice, suggesting that Nrf2 is a primary target of Keap1. The Nrf2-Keap1 system is now recognized as one of the major cellular defence mechanisms against oxidative and xenobiotic stresses. Furthermore, extensive studies have suggested that the Nrf2-Keap1 system contributes to protection against various pathologies, including carcinogenesis, liver toxicity, respiratory distress and inflammation.
authors.affiliation: Center for Tsukuba Advanced Research Alliance, Exploratory Research for Advanced Technology-Japan Science and Technology Corporation, University of Tsukuba, Tsukuba 305-8577, Japan.
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D008658:Inactivation, Metabolic / Q000235:genetics / Q000502:physiology; D000072019:Kelch-Like ECH-Associated Protein 1; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D051267:NF-E2-Related Factor 2; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology*; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D015262:Xenobiotics