More importantly, the POMP-ARE mutation impaired the NRF3-mediated reduction of Rb protein levels, irrespective of TAK-243 treatment (Fig. 5A, right, parental oeNRF3#2 versus POMP-ARE mutant mtPOMP-oeNRF3#2), suggesting that the upregulation of the NRF3-POMP axis leads to the ubiquitin-independent proteolysis of Rb and p53 in cancer cells. This evidence concerns the gene RB1 and cancer.