| 研究実績の概要 |
The aim of this project was to gain a new insight into the mechanism of regulation of Nrf2 by Keap1. As we have already completed the evaluation of the Dual ETGE Nrf2 knockin-mouse, and have published our analysis of the Keap1-Nrf2-Cul3 complex, for the final phase of the project I tried to use more advanced molecular techniques which would provide a unique perspective on the Keap1-Nrf2 system. To achieve this aim, I tried using a NMR approach to study Keap1 molecular dynamics, but the labelling of Keap1 with the NMR probe proved to be very challenging. As an alternative technique, we also tried to establish a collaboration with Dr. Uchiyama at Osaka University to analyse Keap1 using hydrogen deuterium exchange mass spectrometry (HDX-MS). Unfortunately, the logistics of the collaboration could not be perfected, and therefore I have found a new international collaborator with whom to study the mechanism of Keap1 inactivation by cellular stress.
Future Plan- I have established a collaboration with Dr. Chung in Korea to use HDX-MS to study the Keap1-Nrf2 system in both the basal and stressed states. I will visit Dr. Chung’s lab next month, and we plan to begin generating data together in the near future.
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