Related Experiment Video
Updated: Jul 18, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Mechanistic studies of the Nrf2-Keap1 signaling pathway
1Department of Pharmacology and Toxicology, College of Pharmacy, the University of Arizona, Tucson, Arizona 85721, USA. dzhang@pharmacy.arizona.edu
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 protection against many human diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, acute and chronic lung injury, autoimmune diseases, and inflammation. Therefore, understanding of Nrf2 regulation is crucial in the development of drugs for therapeutic intervention. This review will discuss recent progress in the field of the Nrf2-Keap1 signaling pathway, with emphasis on the mechanistic studies of Nrf2 regulation by Keap1, oxidative stress, or chemopreventive compounds.
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
MAPK Signaling Cascades
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response
Amplifying Signals via Enzymatic Cascade