Mechanistic Studies of the Nrf2-Keap1 Signaling Pathway

TLDR: Recent progress in the field of the Nrf2-Keap1 signaling pathway is discussed, with emphasis on the mechanistic studies of NRF2 regulation by Keap1, oxidative stress, or chemopreventive compounds.

Abstract: Since eukaryotic cells constantly encounter various environmental insults, they have evolved defense mechanisms to cope with toxicant- and carcinogen-induced oxidative stress or electrophiles. One of the most important cellular defense mechanisms against oxidative stress or electrophiles is mediated by the transcription factor Nrf2. Under the basal condition, Nrf2-dependent transcription is repressed by a negative regulator Keap1. When cells are exposed to oxidative stress, electrophiles, or chemopreventive agents, Nrf2 escapes Keap1-mediated repression and activates antioxidant responsive element (ARE)-dependent gene expression to maintain cellular redox homeostasis. Beyond its antioxidant function, Nrf2 has recently been recognized as a key factor regulating an array of genes that defend cells against the deleterious effects of environmental insults. Since this Nrf2-dependent cellular defense response is able to protect multi-organs or multi-tissues, activation of Nrf2 has been implicated in conferring ...