Fig. 1: Post-translational modifications (PTMs) and epigenetic regulation of NRF2 in the antioxidant response.

Under basal conditions, NRF2 is ubiquitinated by the Keap1-Cul3 complex for degradation. During oxidative stress, it dissociates from Keap1, translocates to the nucleus, and activates ARE-driven antioxidant genes like SOD, CAT, and NQO1 to reduce ROS. Key PTMs include phosphorylation (activation), acetylation (enhanced transcription), deacetylation (repression), ubiquitination (degradation), and deubiquitination (stabilization), along with SUMOylation, glycosylation, and PARylation. Epigenetically, DNA methylation represses NRF2, while demethylation enhances its transcription.