NFE2L2 (NRF2)

NRF2, encoded by NFE2L2, is a bZIP transcription factor that commands the cell’s antioxidant and detoxification program: the response to oxidative and electrophilic stress.

Function

Under basal conditions NRF2 is trapped in the cytoplasm by KEAP1, which recruits the CUL3 ubiquitin ligase and keeps the protein degraded with a half-life under half an hour. Reactive oxygen species and electrophiles modify cysteines on KEAP1, the trap releases, and NRF2 accumulates and enters the nucleus. There it binds antioxidant-response elements and induces the protective program: glutathione synthesis, NADPH generation, heme oxygenase-1, glutathione S-transferases, and proteasome subunits. The system is a graded thermostat for