Multiple roles of Nrf2-Keap1 signaling: Regulation of development and xenobiotic response using distinct mechanisms

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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.

Original languageEnglish (US)
JournalFly
Volume8
Issue number1
StatePublished - 2014

Bibliographical note

Funding Information:
I thank Dr Tom Kerppola for critical comments and suggestions. I thank Anna Maurer for proofreading of the manu script. This work was supported by the National Institute on Drug Abuse (T.K. DA030339) and by a fellowship from the University of Michigan Center for Organogenesis to H.D.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Cancer
  • Development
  • Keap1/dKeap1
  • Nrf2/CncC
  • Steroid hormone
  • Transcriptional regulation
  • Xenobiotic response

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