Two-site substrate recognition model for the Keap1-Nrf2 system: A hinge and latch mechanism

Kit I. Tong, Akira Kobayashi, Fumiki Katsuoka, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

404 Citations (Scopus)


Cells are equipped with a number of transcriptional factors that safeguard against various environmental insults. Proteasomal protein degradation plays an important role in the Keap1-Nrf2 cytoprotection system, with molecular machinery similar to that for other environmental defense systems such as inflammatory and hypoxic responses. While Nrf2 protein stabilization is known to be redox-sensitive, the transcription factors NF-κB and HIF-1α for inflammatory and hypoxic responses, respectively, are also influenced by the cellular redox conditions. In this review we present the recently proposed two-site substrate recognition model of the Keap1-Nrf2 system, which regulates the cellular responses against oxidative and xenobiotic stresses. The implications of two destructive motifs in Nrf2, the ETGE and DLG motifs, which appear to function as a hinge and latch attenuating Keap1 activity in different redox states, are discussed.

Original languageEnglish
Pages (from-to)1311-1320
Number of pages10
JournalBiological Chemistry
Issue number10-11
Publication statusPublished - 2006 Oct 1


  • CUL3-BTB E3 ligase
  • DLG motif
  • ETGE motif
  • Keap1
  • Nrf2
  • Oxidative stress sensor


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