| FBB1 | |
| Project ID |  FBB1 [Protein] |
| Project Theme | Structural Basis of Sensor System for Cytoprotective Gene Expression Responding to Carcinogens and Oxidative Stress |
| Project Theme (short) | Stress response sensor |
| Principal Investigator | Masayuki Yamamoto |
| Affiliation | Graduate School of Medicine, Tohoku University |
| Backgrounds | - Biological systems possess their abilities to sense oxidative stress and to detoxify the stress-induced damage - Oxidative stress sensor protein Keap1 induces a transcription factor Nrf2 to activate detoxication enzymes - Elucidation of the molecular mechanism of the Nrf2-Keap1 regulatory system could lead to therapeutics developments for cancers and metabolic diseases |
| Highlights | - Keap1 was found to be a forked-stem dimer structure with two large spheres, resembling a cherry-bob. The two-site binding results in stabilization of Nrf2 - While the Keap1-Nrf2 system is cytoprotective in normal cells, we have shown that constitutive Nrf2 activation affords cancer cells with protection from chemotherapeutic reagents |
| Outline | The antioxidant response is important for the amelioration of oxidative stress. Oxidative stress can result in cancer, cardiovascular diseases and diabetes. Nrf2-Keap1 system plays a significant physiological role in combating oxidative stress, thereby activating the body’s own protective response. Keap1 is an oxidative stress sensor protein and Nrf2 is a master regulator of the antioxidant response. Under normal or unstressed conditions, Keap1 suppresses Nrf2 in the cytoplasm. Oxidative stress disrupts the suppression by Keap1, resulting in a build-up of Nrf2. Unbound Nrf2 is then able to translocate into the nucleus, where it will induce many cytoprotective genes including antioxidative enzymes and detoxication enzymes. In this project, we will elucidate the detailed molecular mechanism of the Nrf2-Keap1 regulatory system in terms of functions and structures. |
| Review | Toxicol. Appl. Pharmacol. Antioxid. Redox Signal. Genes Cells |
| CSML File | FBB1.csml |