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. 2023 Mar 27;46(3):133–141. doi: 10.14348/molcells.2023.0028

Fig. 2. Floodgate Model for the KEAP1-mediated Activation of NRF2.

Fig. 2

In the basal state, the ubiquitin ligase KEAP1-CUL3 complex acts as a floodgate and ubiquitinates NRF2. Ubiquitinated NRF2 degrades through the proteasome system. In response to oxidative and electrophilic stimuli, NRF2 accumulates significantly in the nucleus. These stimuli do not affect the abundance and subcellular localization of KEAP1 and CUL3. NRF2 dimerizes with one of the small MAF proteins (sMAF) to form an NRF2-sMAF heterodimer that recognizes the CNC-sMAF binding element (CsMBE) and activates target gene expression. KEAP1, Kelch-like ECH-associated protein 1; NRF2, NF-E2-related factor 2; CUL3, CULLIN 3; CNC, cap-n-collar.