Upon oxidative/electrophilic stress, Nuclear factor erythroid 2-related NFE2L2 (NRF2) translocates from the cytoplasm to the nucleus and transactivates EpRE-containing genes. The mechanism by which NFE2L2:KEAP1 complex senses the oxidative stress and triggers NFE2L2 release is unclear. It has been proposed that KEAP1, which is rich in reactive cysteines, may directly sense the oxidative stress vio thiol modification and undergo conformational change that releases NFE2L2 (Itoh et al. 1999). The reactive cysteine residues with in KEAP1 undergo oxidation and form an intramolecular disulfide bond. Human KEAP1 has 27 cysteine residues and among those C257, C273, C288 and C297 are most reactive and can be oxidized. C273 of one KEAP1 molecule probably bridge with C288 of a second to form intermolecular disulfide bridges (Zhang & Hannink 2003, Wakabayashi et al. 2004).