The NRF2 transcription factor regulates a major environmental and oxidative stress
response. NRF2 is itself negatively regulated by KEAP1, the adaptor of a Cul3-ubiquitin
ligase complex that marks NRF2 for proteasomal degradation by ubiquitination. Electrophilic
compounds activate NRF2 primarily by inhibiting KEAP1-dependent NRF2 degradation,
through alkylation of specific cysteines. We have examined the impact on KEAP1 of reactive
oxygen and nitrogen species, which are also NRF2 inducers. We found that in untreated …