Nrf2MafG

Nrf2MafG refers to the transcription factor complex formed by Nrf2 (nuclear factor erythroid 2–related factor 2) and MafG, a small Maf protein. This heterodimer binds to antioxidant response elements (ARE) in the promoters of cytoprotective genes and coordinates their transcription in response to oxidative stress and electrophilic challenge.

Nrf2 is a CNC-bZIP transcription factor that is regulated by the Keap1-CUL3 ubiquitin ligase complex. In resting cells, Nrf2 is targeted for degradation; under oxidative or electrophilic stress, Nrf2 is stabilized and translocates to the nucleus, where it dimerizes with MafG. The Nrf2-MafG complex recognizes ARE motifs and promotes transcription of genes involved in antioxidant defense and detoxification.

Target genes commonly regulated by the Nrf2-MafG complex include those responsible for glutathione synthesis (GCLC and GCLM), detoxification (NQO1), heme metabolism (HMOX1), and various phase II enzymes such as glutathione S-transferases. Through these actions, the complex helps maintain redox homeostasis, supports cellular defense against electrophiles, and modulates inflammatory responses.

Biological and clinical relevance is broad. The pathway contributes to aging, neuroprotection, and metabolic regulation, and it has been implicated in cancer biology. In cancer, sustained Nrf2 activity can promote tumor cell survival and chemoresistance, while in other contexts it offers cytoprotection. MafG can pair with other small Maf proteins, influencing ARE binding and target gene selection in a context-dependent manner.