Fig. 2: Domain structure of NRF2 and its regulatory interactions.

The Neh2 domain binds Keap1 via the DLG and ETGE motifs, regulating NRF2 stability. Neh4 and Neh5 facilitate transcriptional activation by interacting with co-activators such as HRD1 and CBP. Neh7 inhibits NRF2 via interaction with RXRα, Neh6 promotes degradation through the DSGIS and DSAPGS motifs, interacting with β-TrCP and GSK3β. The Neh1 domain contains the CNC-bZIP motif for DNA binding and dimerization, and Neh3 supports transcriptional activation.