MBB External Lunch Seminar
Molecular Mechanism of Environmental Stress Response
Speaker: Dr. Masayuki Yamamoto, MD PhD (Professor and Chairman, Department of Medical Biochemistry, Tohoku University Graduate School of Medicine / School of Medicine, and Executive Director Tohoku Medical Megabuck Organization)
Host: Elias Arnér (MBB, Div. of Biochemistry)
Abstract: Our body equips a cytoprotective system that senses environmental insults and activates cellular defense enzyme genes. Transcription factor Nrf2 is essential for the coordinated induction of cellular defense enzymes. This notion has been best demonstrated in animal models, showing that Nrf2-null mice are sensitive to a wide variety of electrophiles and ROS. Keap1 is a component of ubiquitin-E3 ligase that degrades Nrf2 constitutively. Keap1 possesses reactive cysteine residues that act as sensors for electrophilic and oxidative stresses. We refer to this system as the Cysteine Code. The two-site recognition model proposed for the Keap1-Nrf2 system describes the mechanism of nuclear accumulation of Nrf2 in a Cul3-Keap1 E3 ubiquitin ligase-dependent manner. This model has been verified through structure biology, mouse/zebrafish genetics, and human cancer analyses. The Keap1-Nrf2 system opens a new avenue to the understanding of the signal transduction and regulatory processes underlying the stress response.