Fig. 1

Structural domains of Nrf2 and Keap1. Nrf2 contains an N-terminal hydrophobic domain, followed by a Keap1-binding domain, transcriptional activation domain, CNC domain, and basic and leucine zipper domains. Nrf2, through its leucine zipper domain, heterodimerizes with small Maf or Jun proteins and binds to the ARE. Keap1, a homodimeric protein, retains Nrf2 in the cytoplasm. Keap1 functions as an adaptor for Cul3/Rbx1-mediated degradation of Nrf2. Keap1 with its BTB domain binds to Rbx1-bound Cul3, and its double-glycine repeat/Kelch (DGR) domain binds to Nrf2 and subsequently causes ubiquitination and degradation of Nrf2. BTB and DGR domains are separated by the intervening region (IVR)