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Molecular and structural analyses of Nrf2 signaling uncovered a “dedepression” regulatory mechanism, wherein Nrf2 is suppressed under a basal condition through Keap1 (Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1)-dependent ubiquitination-proteasomal degradation and is activated by oxidants and electrophiles via modification of critical cysteine thiols of Keap1 and Nrf2 (18)