KEAP1 and lung cancer: For example, gain-of-function mutations within the Keap1-binding domain of Nrf2, specifically within the DLG motif (e.g. L30F) and ETGE motif (e.g. T80R), impair its recognition by Keap1-Cul3, leading to the dysregulation and subsequent hyperactivation of Nrf2 in lung cancer (Shibata et al., 2008).