Regulation of transcription factor Nrf2 activity by the stress sensor Keap1

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Tohoku University
• Principal Investigator: Suzuki Takafumi 東北大学, 医学系研究科, 准教授 (70508308)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Keap1

Outline of Final Research Achievements

Disruption of the response system to oxidative stress is closely related to the development of various diseases. To prevent such diseases, cells respond rapidly to oxidative stress and maintain homeostasis. The stress sensor Keap1 regulates the ubiquitination of the transcription factor Nrf2 and is a key factor that plays a central role in the oxidative stress defense mechanism. In this study, we aimed to identify the reactive oxygen species sensor of Keap1 and elucidate its physiological function, as well as the molecular basis of Nrf2 activation in the oxidative stress response. Furthermore, we aimed to elucidate the molecular mechanism of oxidative stress response by the Keap1-Nrf2 regulatory system through structure-function linkage analysis.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、Keap1が活性酸素種を感知するメカニズムを明らかにしました。このメカニズムは、親電子性物質を感知するメカニズムとは異なり、Keap1はセンサーを使い分けてストレスを感知していることが明らかになりました。本研究を進めていくことで、Keap1－Nrf2システムの活性化メカニズムの分子基盤の理解が進み、Keap1－Nrf2システムを利用した新薬や治療法の開発が加速することが期待されます。