NFE2L2 and cancer: Cancer cells with high nuclear factor erythroid 2-related factor 2 (NRF2) expression levels are less sensitive to chemotherapeutic agents, and multiple RING-type E3 ubiquitin ligase complexes, KEAP1-CUL3-RBX1, β-TrCP-SKP1-CUL1-RBX1, and HRD1, mediate ubiquitination and proteasomal degradation of NRF2, affecting the relationship between NRF2 overexpression and increased 5-FU resistance in CRC (Homma et al. 2009).