Under normal conditions, Keap1, an adaptor protein of Cullin-3
ubiquitin ligase, allows ubiquitination and degradation of NRF2.
OBJECTIVE: We investigated the cross-regulations among NRF2, NRF1, and KEAP1, a cullin-3 adapter protein that allows NRF2 to be ubiquinated and degraded by the proteasome complex, in arsenic-induced antioxidant responses.
Kelch-like ECH-associated protein 1 (KEAP1), a cytoplasmic protein, serves as a substrate-adaptor molecule for cullin-3 based ubiquitin E3 ligase (Kobayashi et al.
Under normal physiological conditions, Keap1, which is also called an inhibitor of Nrf2 (INrf2), is associated with Nrf2 (the majority of which resides in the cytoplasm) and recruits and interacts with the cullin-3 E3-ubiquitin ligase (Cul3) .
Additionally, numerous reports have suggested that Kelch-like ECH-associated protein-1 (Keap1), a substrate adaptor protein for a cullin-3 E3-ubiquitin ligase (Cul3)/Ring-Box1 (Rbx1) dependent complex, plays a critical role in the ubiquitination and degradation of Nrf2, IKK[beta], and Bcl-2/Bcl-xL, also being disturbed by ROS via modifying the reactive cysteines (Cys273, Cys288, and Cys151) and then inducing a conformational change that leads to the release of Nrf2, IKK[beta], and Bcl-2/Bcl-xL from Keap1 and the suspending of their ubiquitination and degradation [172-174].