Q14145

Keap1 (kelch-like ECH-associated protein 1) also known as INrf2, KLHL19 is a stress sensing adaptor for the Cullin3 (Cul3)-dependent E3 ubiquitin ligase complex that negatively regulates Nrf2 (NF-E2-related factor 2). This regulation is vital because Nrf2 is a key transcription factor that mediates the expression of cytoprotective genes in response to oxidative stress and electrophilic insults. Under normal conditions, Keap1 maintains low levels of Nrf2 by promoting ubiquitination and subsequent degradation, thereby preventing excessive activation of protective genes. During oxidative stress, modifications to specific cysteine residues in Keap1, particularly Cys 273 and Cys 288, lead to a conformational change that releases Nrf2, allowing nuclear translocation and target gene activation.