Molecular mechanisms of growth control via TOR complex in response to inputs.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Niigata University
• Principal Investigator: Fukuda Tomoyuki 新潟大学, 医歯学系, 准教授 (90415282)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: TOR / TORC1 / シグナル伝達 / 細胞増殖

Outline of Final Research Achievements

Target of rapamycin complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that controls cell growth and metabolism. To understand the molecular mechanism of TORC1-mediated cell growth control, factors involved in TORC1 signaling have been screened for, identified and characterized using fission yeast as a model. This study has revealed that TORC1 is negatively regulated by three signaling pathways in response to nutrient availability. Moreover, a transcription factor, which regulates genes involved in protein synthesis, has been found to be stabilized by TORC1, suggesting that TORC1 promotes cell growth through the activation of protein synthesis via this transcription factor. Thus, this study provides insights into understanding of the mechanisms by which cells grow in response to nutrients.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は分裂酵母をモデルに、TOR複合体の活性調節に関わる複数の経路と、TOR複合体の下流で増殖を促進する因子とを同定し、それぞれの特徴付けを行った。これらの経路や因子は高度に保存されているため、哺乳類の細胞増殖においてもTOR複合体が同様に制御されていると予想される。TOR複合体経路は多種の癌細胞で過度に活性化しており、癌の進行を促進することが知られている。また、TOR複合体は代謝や老化にも関与する。したがって、本研究で明らかになったTOR複合体の活性制御機構や下流の因子を標的に、抗腫瘍、アンチエイジング、糖尿病、肥満に関連する創薬や治療法の開発につながる可能性がある。