Figure 3. KEAP1-dependent and KEAP1-indepdnednt degradation of NRF2.
KEAP1 serves as an NRF2-recognizing subunit of CUL3-based ubiquitin E3 ligase and leads NRF2 to proteasome-dependent degradation. KEAP1 is inactivated by thiol modification with electrophiles, which allows NRF2 to be translocated to nucleus and activate its target gene transcription. When NRF2 is phosphorylated by GSK3, βTrCP serves as an NRF2-recognizing subunit of CUL1-based ubiquitin E3 ligase.