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Related Experiment Video

Updated: Sep 13, 2025

Monitoring On-Target Signaling Responses in Larval Zebrafish - Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

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Published on: June 2, 2023

Dissecting the Keap1/Nrf2 pathway through proteomics.

Tigist Y Tamir¹, Kathleen M Mulvaney², M Ben Major^1,2

¹Department of Pharmacology and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Current Opinion in Toxicology

|August 1, 2025

Summary

This summary is machine-generated.

Mass spectrometry proteomics reveals the KEAP1/NRF2 antioxidant pathway's complex network. This study maps protein interactions and modifications, offering insights into its regulation and therapeutic potential.

Keywords:

E3 ubiquitin ligase KEAP1 Mass spectrometry NRF2 Oxidative stress Post-translational modification Protein interaction network Proteomics

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Area of Science:

Biochemistry
Molecular Biology
Proteomics

Background:

The KEAP1/NRF2 pathway is crucial for cellular antioxidant defense.
Understanding its regulation is key for developing new therapeutic strategies.
Proteomic technologies offer powerful tools to study this pathway.

Purpose of the Study:

To review and synthesize current knowledge on the KEAP1/NRF2 pathway using mass spectrometry-based proteomics.
To construct protein interaction networks for KEAP1 and NRF2.
To map post-translational modifications on KEAP1 and NRF2.

Main Methods:

Comprehensive literature and public domain data compilation.
Creation of protein-protein interaction networks for KEAP1 and NRF2.
Curation of proteomic datasets to map post-translational modifications.

Main Results:

Identification of numerous associated proteins and post-translational modifications within the KEAP1/NRF2 complex.
Depiction of a highly interconnected signaling network with many proteins of unknown function.
Generation of comprehensive maps of KEAP1 and NRF2 modifications.

Conclusions:

Mass spectrometry is instrumental in elucidating KEAP1/NRF2 pathway signaling and dynamics.
The study highlights potential new regulatory mechanisms and therapeutic targets.
Further research is needed to understand the functional significance of identified modifications and interactions.