title: Multiple roles of Nrf2-Keap1 signaling: regulation of development and xenobiotic response using distinct mechanisms.
abstract: Xenobiotic and oxidative responses protect cells from external and internal toxicities. Nrf2 and Keap1 are central factors that mediate these responses, and are closely related with many human diseases. In a recent study, we revealed novel developmental function and regulatory mechanism of Nrf2 and Keap1 by investigating their Drosophila homolog CncC and dKeap1. We found that CncC and dKeap1 control metamorphosis through regulations of ecdysone biosynthetic genes and ecdysone response genes in different tissues. CncC and dKeap1 cooperatively activate these developmental genes, in contrast to their conserved antagonizing effect to xenobiotic response transcription. In addition, interactions between CncC and Ras signaling in metamorphosis and in transcriptional regulation were established. Here I discuss the implications that place these classic xenobiotic response factors into a broader network that potentially control development and oncogenesis using mechanisms other than those mediating xenobiotic response.
authors.affiliation: Department of Biological Chemistry; University of Michigan Medical School; Ann Arbor, MI USA.
authors.forename: Huai
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004330:Drosophila / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D008675:Metamorphosis, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015262:Xenobiotics / Q000494:pharmacology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527886:Keap1 protein, Drosophila; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D012097:Repressor Proteins; D015262:Xenobiotics; C116463:cnc protein, Drosophila; D004440:Ecdysone; D018631:ras Proteins
keywords: Keap1/dKeap1; Nrf2/CncC; cancer; development; steroid hormone; transcriptional regulation; xenobiotic response