fig3

Figure 3. Redox regulation of NRF2-KEAP1 signalling. A: Under normal physiological (homeostatic) conditions, KEAP1 interacts with NRF2 in the cytosol, promoting its polyubiquitylation and subsequent proteasomal degradation by the substrate adaptor for cullin-based E3 ubiquitin ligase complex, resulting in little NRF2 that is sufficient for the maintenance of cellular homeostasis or absence of NRF2 transactivation; B: In contrast, under oxidative stress conditions, the binding of KEAP1 to NRF2 is greatly impaired to compromise the likelihood of NRF2 ubiquitylation. Consequentl, a greater fraction of NRF2 molecules in the cytosolic pool can translocate into the nucleus, wherein NRF2 interacts with sMAF proteins, then binds to DNA and other transcription partners to form a heterodimeric nuclear complex, which induces the transcription of several antioxidant and cytoprotective genes. NRF: nuclear factor E2-related factor 2; sMAF: small musculoaponeurotic fibrosarcoma