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 establish and characterize yeast models expressing human Nrf2, 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 novel insight into the crosstalk between the antioxidant response and the heat shock response.

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