A Naturally-Occurring Dominant-Negative Inhibitor of Keap1 Competitively against Its Negative Regulation of Nrf2.

ABSTRACT: Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) is a master regulator of antioxidant and/or electrophile response elements (AREs/EpREs)-driven genes involved in homeostasis, detoxification, and adaptation to various stresses. The cytoprotective activity of Nrf2, though being oppositely involved in both cancer prevention and progression, is critically controlled by Keap1 (Kelch-like ECH-associated protein 1), which is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase and also is a key sensor for oxidative and electrophilic stresses. Here, we first report a novel naturally-occurring mutant of Keap1, designated Keap1^ΔC, which lacks most of its C-terminal Nrf2-interacting domain essential for inhibition of the cap'n'collar (CNC) basic-region leucine zi

SUBMITTER: Qiu L 

PROVIDER: S-EPMC6122090 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature