Molecular Basis of the KEAP1-NRF2 Signaling Pathway

Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal…

• SM
  Suzuken Memorial Foundation
• TS
  Takeda Science Foundation
• JA
  Japan Agency for Medical Research and Development

  Awards: JP22ama121038, 19H05649
• MO
  Ministry of Education, Culture, Sports, Science and Technology

  Award: 19H05649
• MM
  Mochida Memorial Foundation for Medical and Pharmaceutical Research
• FF
  Foundation for Promotion of Cancer Research
• LS
  Life Science Foundation of Japan
• JS
  Japan Society for the Promotion of Science

  Awards: JP22ama121038, 19H05649, 22K06876