CUL3 and cancer: The modulation of NRF2 activity is predominated by the adjustment of NRF2 protein stability and degradation as opposed to transcriptional expression changes of the NFE2L2 gene, therefore somatic mutations within genes that encode NRF2 regulatory proteins such as KEAP1 (KEAP1), β-TrCP (BTRC) and CUL3 (CUL3) are common within NRF2-addicted cancers.