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. Author manuscript; available in PMC: 2021 Mar 1.
Published in final edited form as: Arch Pharm Res. 2019 Aug 1;43(3):361–369. doi: 10.1007/s12272-019-01177-2

Figure 1: The NRF2 signaling pathway.

Figure 1:

Under normal conditions, NRF2 is bound by KEAP1 as part of a CUL3-RBX1 complex that facilitates its ubiquitylation and proteasomal degradation. Electrophiles (i.e. sulforaphane [SF]) oxidize key cysteine residues in KEAP1 that causes a conformational change in the NRF2-KEAP1 complex that prevents ubiquitylation of NRF2. Thus, newly synthesized NRF2 accumulates and transcription of its target genes begins (left side). In renal cancers, somatic mutations in KEAP1, CUL3, or NRF2, or post-translational modifications to KEAP1 prevent ubiquitylation of NRF2 and result in constitutive activation of the NRF2 cascade. In this case, NRF2 is constantly transcribing its target genes, thus protecting the cancer cell (right side).