Experimental Animal Division

Nuclear factor, erythroid derived 2, like 2 (Nfe2l2, or Nrf2) is a transcription factor, that serves as a key regulator of the cellular defense against oxidative and electrophilic stresses [1]. Under normal conditions, Nrf2 is rapidly degraded through its association with kelch-like ECH-associated protein 1 (Keap1). Upon exposure to oxidative and electrophilic stress, the reactive cysteine residues of Keap1 become modified, liberating Nrf2 from its Keap1-mediated degradation. Polyubiquitin-binding protein p62 also interacts with the Nrf2-binding site on Keap1, resulting in the stabilization of Nrf2 [2].

Nrf2-regulated cytoprotective genes include heme oxygenase-1 (HO-1) and glutathione S-transferase (GST). The target genes are involved in elimination of reactive oxygen species (ROS), glutathione synthesis, foreign material metabolism, and drug transport. Nrf2 deficiency in mice increases their sensitivity to cigarette smoke, lipopolysaccharides, high-fat diet, and UV irradiation. Missense mutations in NRF2 and KEAP1 have recently been identified in many types of human cancer. Nrf2-deficient mice exhibit increased susceptibility to lung metastasis, which is associated with greater inflammation [3]. Different strains of Nrf2-deficient mice will provide the opportunity to understanding the role of Nrf2 in various common diseases.