KEAP1 and neoplasm: To regulate ROS homeostasis, tumor cells need to activate anti-oxidative stress (AOS) response elements, mainly through NRF2 activation, a transcription factor encoded by the gene NFE2L2. At basal levels, NRF2 is bound to its repressor, Kelch-like ECH-associated protein 1 (KEAP1), which drives its ubiquitination by CUL3 and subsequent degradation in the proteasome.