Significantly, aberrant accumulation of Nrf2 and activation of target genes are significantly incremented by simultaneous deletion of PTEN (leading to a GSK3β-directed phosphodegron of Nrf2 targeting this CNC-bZIP protein to the β-TrCP-based E3 ubiquitin ligase Cullin 1-mediated proteasomal degradation) and Keap1 (acting as an adaptor targeting Nrf2 to the Cullin 3-mediated proteasomal degradation), resulting in a deterioration of PTEN−/−-leading cancer pathology [19,20,21]. The gene discussed is BTRC; the disease is cancer.