MAFFNrf2

MAFFNrf2 refers to the transcriptional complex formed by MAFF, a small Maf family member, and Nrf2, the master regulator of the antioxidant response. MAFF belongs to the Maf family that forms dimers with other basic leucine zipper proteins; in the context of oxidative stress, MAFF dimerizes with Nrf2 to enable binding at antioxidant response elements (ARE) in target gene promoters.

Mechanism: Under basal conditions, Nrf2 is kept at low levels by Keap1-mediated ubiquitination. Upon oxidative or electrophilic stress, Nrf2 stabilizes, translocates to the nucleus, and heterodimerizes with MAFF to form the MAFFNrf2 complex. The complex recognizes ARE sequences and drives transcription of a broad set of cytoprotective genes, including GCLC and GCLM (glutamate–cysteine ligase), NQO1, HMOX1 (HO-1), GSTs, and other genes involved in glutathione metabolism, detoxification, and redox balance.

Roles: The MAFFNrf2 complex contributes to cellular defense against oxidative damage, xenobiotics, and inflammation; it also influences detoxification capacity and can modulate sensitivity to chemotherapeutics. In disease contexts, dysregulation of this pathway can impact cancer progression, neurodegeneration, and aging.

Regulation and diversity: The small Maf proteins MAFF, MAFG, and MAFK can substitute for one another as Nrf2 partners, shaping gene-specific transcription. MAFF contributes via its basic region-leucine zipper, while Nrf2 provides transactivation domains. Coactivators such as CBP/p300 may be recruited, and post-translational modifications or signaling pathways can influence the activity of the MAFFNrf2 complex.

Note: MAFFNrf2 is not a separate gene or protein but a functional transcriptional complex; literature often refers to MAFF–Nrf2 or Nrf2–MAFF interactions. See also Nrf2, Keap1, ARE.