Quantitative understanding of the mechanism of G1-S phase checkpoint regulated by ERK signal

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02444
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Center for Novel Science Initatives, National Institutes of Natural Sciences
• Principal Investigator: AOKI Kazuhiro 大学共同利用機関法人自然科学研究機構(新分野創成センター、アストロバイオロジーセンター、生命創成探究, 生命創成探究センター, 教授 (80511427)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ERK / Akt / 光遺伝学 / 細胞周期 / チェックポイント

Outline of Final Research Achievements

The cell cycle, which determines whether cells divide or not, is an essential mechanism for living organisms. In this study, the activities of ERK and Akt, which are activated downstream of growth factors, were visualized at the single cell level by live-cell imaging, and the effects of their dynamics on the cell cycle were analyzed. We found that, (1) Akt shows a stochastic activation patterns similar to ERK, (2) there is a strong correlation between the activities of ERK and Akt, but there is a difference between them especially in the S phase, and (3) Akt activity is necessary for S/G2 progression, and (4) endocycling, which is a cell cycle progression without cytokinesis, occurs by inhibiting both ERK and Akt.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞の分裂、増殖は胚発生や再生といった生理的なプロセスと悪性腫瘍の増殖といった病理的な側面で起こる現象であり、細胞分裂を制御する細胞周期の理解は極めて重要である。本研究では、ERKとAktというどちらも多くの悪性腫瘍細胞で活性化が認められるシグナル伝達分子の細胞周期の役割を生細胞イメージングによってアプローチした研究であり、これまで知られていない結果を得ることができた。特に、Aktの細胞周期における役割のいくつかを今回の研究で明らかにすることができたことは今後の悪性腫瘍の治療戦略を考えるうえで重要になってくるものと考える。