Fig. 3: Ubiquitination pathways regulating NRF2 degradation.

The KEAP1-Cul3 complex ubiquitinates NRF2 via the Cul3-PBX1 complex, targeting it for proteasomal degradation. The β-TrCP-Cul1 complex, activated by GSK-3-mediated phosphorylation of NRF2, promotes its ubiquitination and degradation. The Hrd1 pathway directly ubiquitinates NRF2 through the Hrd1 E3 ligase. The WDR23-Cul4-DDB1 complex facilitates NRF2 ubiquitination and degradation.