Regulation of transcription factor Nrf2 activity by the stress sensor Keap1

2021 Fiscal Year Final Research Report

• Project/Area Number: 17KK0183
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• 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): 2018 – 2021
• Keywords: ストレス応答

Outline of Final Research Achievements

Nrf2 is a transcription factor that acts as defense system by regulating a group of genes involved in oxidative stress and xenobiotic metabolism. Keap1 functions as a sensor molecule and stops the ubiquitination reaction of Nrf2 when Keap1 senses oxidative stress. Stabilized Nrf2 accumulates in the nucleus and activates transcription of various target genes. In this study, we aim to elucidate the molecular basis of Nrf2 activation in the stress response, especially the regulation mechanism of ubiquitination by Keap1.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、Keap1-Nrf2タンパク質相互作用を阻害する化合物がNrf2活性化を引き起こすメカニズムとその影響を明らかにすることに成功した。これまでは試験管内反応においてのみ解析が実施されてきたが、本研究により、細胞レベルおよびマウス個体レベルでの実証に成功した。この研究成果は、Keap1-Nrf2タンパク質相互作用阻害による次世代型のNrf2活性剤の開発に有益な情報を提供する。