Nuclear factor erythroid 2-related factor 2 (encoded by NFE2L2) (Nrf2)

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene that acts as a master regulator of cellular defense against oxidative and electrophilic stress by inducing the expression of a broad array of cytoprotective genes, including those involved in antioxidant response and detoxification. Under homeostatic conditions, Nrf2 is negatively regulated by Keap1-mediated ubiquitination and proteasomal degradation. Upon exposure to oxidative or electrophilic stress, Nrf2 is released from repression, translocates to the nucleus, dimerizes with small Maf proteins, and activates the transcription of target genes via antioxidant response elements (AREs). Nrf2 is implicated in many diseases—its activation is beneficial in chronic inflammatory or neurodegenerative diseases, but persistent activation can also support carcinogenesis and chemoresistance.

Other names

Nuclear factor (erythroid-derived 2)-like 2NF-E2-related factor 2NFE2L2 (gene name)

Activation of Nrf2 pathway (by stabilizing Nrf2 protein or inhibiting its repressor Keap1, leading to induction of cytoprotective and antioxidant genes); Inhibition of Nrf2 (as a strategy in certain cancers with aberrant Nrf2 activation)