The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

The KEAP1-NRF2 pathway is the principal protective response to oxidative and electrophilic stresses. Under homeostatic conditions, KEAP1 forms part of an E3 ubiquitin ligase, which tightly regulates the activity of the transcription factor NRF2 by targeting it for ubiquitination and proteasome-dependent degradation. In response to stress, an intricate molecular mechanism facilitated by sensor cysteines within KEAP1 allows NRF2 to escape ubiquitination, accumulate within the cell, and translocate to the nucleus, where it can promote its antioxidant transcription program. Recent advances have revealed that KEAP1 contains multiple stress sensors and inactivation modalities, which together allow diverse cellular…

• JA
  Japan Agency for Medical Research and Development

  Awards: JP19cm0106101, JP17am0101001
• JS
  Japan Society for the Promotion of Science

  Awards: 19K16512, 19H05649