FIG. 8.

Schematic model of the Keap1-Cul3 complex function as an E3 ligase. The cytoplasmic factor Keap1, bound on actin filaments, acts as a sensor for oxidative and electrophilic stress through two cysteine residues in the IVR domain. In the absence of stimuli, Keap1 sequesters the transcription factor Nrf2, a major regulator of the oxidative stress response, in the cytoplasm. In addition, Keap1 functions as an adaptor of the Cul3-based E3 ligase. This E3 ligase conjugates ubiquitin to Nrf2 and promotes rapid degradation of Nrf2 by proteasome in order to inhibit the expression of oxidative stress response genes under normal conditions.