The substrate adaptor protein Keap1 has emerged as a key sensor for oxidative stress and electrophilic molecules. Initially, the Keap1 gene KIAA0132 was mapped to chromosome 19 (Nagase et al. 1995) and later identified by yeast-two hybrid screening as an interacting partner of Nrf2 (transcription factor). Keap1 was named so due to its homology to the actin binding egg-chamber regulatory protein “Kelch” in Drosophila. It was found to be a major negative regulator of Nrf2-mediated transactivation of ARE-dependent proteins (Itoh et al. 1999). Subsequent research facilitated understanding the role of Keap1 in Nrf2 ubiquitination, proteasomal degradation, and its dysregulation. Mice with Keap1 null mutation presented with postnatal lethality due to severe hyperkeratotic constrictions in the esophagus and forestomach; at the cellular level, absence of Keap1 resulted...
- Dieter BP. Dysregulation of Nrf2 signaling in diabetes: an opportunity for a multitarget approach. J Diab Metabol. 2015;6:475.Google Scholar
- Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213–23.PubMedCentralPubMedCrossRefGoogle Scholar