title: Conservation of the Keap1-Nrf2 System: An Evolutionary Journey through Stressful Space and Time.
abstract: The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as zebrafish, fruit fly andCaenorhabditis elegans, have been shown to have similar anti-stress systems to mammals, suggesting that analogous defense systems are widely conserved throughout the animal kingdom. Experimental evidence in lower animals provides important information beyond mere laboratory-confined utility, such as regarding how these systems transformed during evolution, which may help characterize the mammalian system in greater detail. Recent advances in genome projects of both model and non-model animals have provided a great deal of useful information toward this end. We herein review the research on Keap1-Nrf2 and its analogous systems in both mammals and lower model animals. In addition, by comparing the amino acid sequences of Nrf2 and Keap1 proteins from various species, we can deduce the evolutionary history of the anti-stress system. This combinatorial approach using both experimental and genetic data will suggest perspectives of approach for researchers studying the stress response.
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. fuse_yuji@md.tsukuba.ac.jp.|Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan. fuse_yuji@md.tsukuba.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fuse
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. makobayash@md.tsukuba.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D005075:Biological Evolution; D005786:Gene Expression Regulation; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D013045:Species Specificity; D013312:Stress, Physiological; D013329:Structure-Activity Relationship
chemical_list: D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2
keywords: C. elegans Skn-1; Drosophila Cnc; Hydra Nrf; Keap1; Nrf2; anti-stress system; evolutionary history; mouse; yeast Yap1; zebrafish