A novel yeast model detects Nrf2 and Keap1 interactions with Hsp90

• Published in: Disease models & mechanisms Vol. 15; no. 4
• Main Authors: Ngo, Vy, Brickenden, Anne, Liu, Hansen, Yeung, Cynthia, Choy, Wing-Yiu, Duennwald, Martin L
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-04-2022; The Company of Biologists
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Apoptosis; Cell cycle; Cyclin-dependent kinases; Genes; Genotype & phenotype; hsp90; Humans; keap1; Kelch-Like ECH-Associated Protein 1; Localization; Microscopy; molecular chaperones; Mutation; NF-E2-Related Factor 2 - metabolism; nrf2; Oxidative Stress; Protein expression; protein interactions; Protein-Folding Diseases: Models & Mechanisms; Proteins; Saccharomyces cerevisiae - metabolism; Toxicity; Yeast; yeast model; Hsp90; Keap1; Molecular chaperones; Nrf2; Protein interactions; Yeast model
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.049258

Nrf2 is the master transcriptional regulator of cellular responses against oxidative stress. It is chiefly regulated by Keap1, a substrate adaptor protein that mediates Nrf2 degradation. Nrf2 activity is also influenced by many other protein interactions that provide Keap1-independent regulation. To study Nrf2 regulation, we established and characterized yeast models expressing human Nrf2 (also known as NFE2L2), Keap1 and other proteins that interact with and regulate Nrf2. Yeast models have been well established as powerful tools to study protein function and genetic and physical protein-protein interactions. In this work, we recapitulate previously described Nrf2 interactions in yeast and discover that Nrf2 interacts with the molecular chaperone Hsp90. Our work establishes yeast as a useful tool to study Nrf2 interactions and provides new insight into the crosstalk between the antioxidant response and the heat shock response.