Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that plays a central role in cellular defense against oxidative and electrophilic stress. It regulates the expression of genes containing antioxidant response elements (AREs), leading to increased production of cytoprotective proteins. Nrf2 influences metabolism, inflammation, autophagy, proteostasis, mitochondrial function, and immune responses. Dysregulation of Nrf2 is implicated in diseases such as cancer, atherosclerosis, and liver injury. Therapeutic strategies are being explored to modulate Nrf2 activity.

Other names

NFE2L2NRF₂NF-E₂-related factor ₂

Under non-stressed conditions, Keap1 binds to the Neh2 domain on Nrf2, promoting ubiquitination and degradation. Upon oxidative/electrophilic stress, Keap1 is modified/inhibited, releasing Nrf2. Stabilized Nrf2 accumulates/translocates into the nucleus, forms heterodimers with small Maf proteins, binds ARE sequences on DNA promoters, and initiates transcription of cytoprotective/antioxidant/detoxification genes.