Time-dependent adaptation system coordinated by protein modification/binding oscillator

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Toho University
• Principal Investigator: TAMARU Teruya 東邦大学, 医学部, 講師 (80291706)
• Co-Investigator(Renkei-kenkyūsha): Hattori Mitsuru 東京大学, 理学系研究科, 特任研究員 (20589858)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: circadian rhythm / clock gene / phosphorylation / p53 / Bioluminescence / heat shock / stress response / UV

Outline of Final Research Achievements

Disorder of biological clocks cause /exacerbate lifestyle-related diseases and cancers. Daily oscillating circadian adaptation system (CAS) with synchronizing ability to environments, based on molecular clocks with clock genes, e.g., Bmal1, integrate timings of various physiological functions in whole body, and to coordinate anti-diseases adaptation systems. In this study, I first elucidated oscillatory mechanism for circadian phosphorylation of BMAL1 clock protein, the core of protein modification /binding oscillators to drive CAS. Additionally, I investigated behavior and structural basis for time-dependent crosstalk by networking among transcription factors BMAL1, heat-shock responsive HSF1 and tumor-suppressor p53 during UV-triggered clock synchronization, to elucidate activation mechanism of CAS in response to cell stresses. The achievements lead to novel medicine targeted to CAS.

Free Research Field

時間生物学