Roles of stress-responsive transcription factors in health and disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249015
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: YAMAMOTO Masayuki 東北大学, 医学(系)研究科(研究院), 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): KATSUOKA Fumiki 東北大学, 東北メディカルメガバンク機構, 准教授 (30447255)
• Co-Investigator(Renkei-kenkyūsha): URUNO Akira 東北大学, 大学院医学系研究科, 講師 (90396474) ; SUZUKI Norio 東北大学, 大学院医学系研究科, 講師 (20447254)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 酸化ストレス / 転写制御

Outline of Final Research Achievements

Transcription factor Nrf2 regulates a broad cytoprotective response to environmental stresses through induction of cellular defense enzymes. Keap1 is an adaptor protein for cullin3-based ubiquitin E3 ligase and negatively regulates Nrf2. This notion has been best demonstrated in animal models, showing that Nrf2-null mice are sensitive to a wide variety of electrophiles and reactive oxygen species (ROS). Keap1 possesses reactive cysteine residues that act as sensors for electrophilic and oxidative stresses. We have verified this model through structure biology, mouse/zebrafish genetics, and human cancer analyses. Elevated expression of NRF2 target genes confers advantages on the growth of cancer cells through the metabolic reprogramming. Thus, the Keap1-Nrf2 system opens a new avenue to the understanding of the signal transduction and regulatory processes underlying the stress response and cancer progression.

Free Research Field

生化学・分子生物学