Description
KELCH-LIKE ECH-ASSOCIATED PROTEIN 1 is a protein that in humans is encoded by the KEAP1 gene. Keap1 contains a central BTB/POZ domain and a C-terminal double glycine repeat (DGR), or Kelch, module. Keap1 has been shown to interact with Nrf2, a master regulator of the antioxidant response, which is important for the amelioration of oxidative stress. In the presence of the electrophilic agent diethylmalate, Nrf2 activity is released from Keap1 and Nrf2 translocate to the nucleus. Under quiescent conditions, Nrf2 is anchored in the cytoplasm through binding to Keap1, which, in turn, facilitates the ubiquitination and subsequent proteolysis of Nrf2. Because Nrf2 activation leads to a coordinated antioxidant and anti-inflammatory response, and Keap1 represses Nrf2 activation, Keap1 has become a very attractive drug target