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Licensed Unlicensed Requires Authentication Published by De Gruyter November 2, 2006

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

Kit I. Tong, Akira Kobayashi, Fumiki Katsuoka and Masayuki Yamamoto
From the journal


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.


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Published Online: 2006-11-02
Published in Print: 2006-10-01

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