2022 Fiscal Year Final Research Report
Molecular basis of substrate phosphorylation by mTORC1
Project/Area Number |
19K06564
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43030:Functional biochemistry-related
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Research Institution | Nara Institute of Science and Technology |
Principal Investigator |
Morozumi Yuichi 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (80571439)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | mTORC1 / 分裂酵母 / ラパマイシン |
Outline of Final Research Achievements |
Evolutionarily conserved mTOR complex 1 (TORC1) is a multi-subunit protein kinase complex that controls cellular growth and metabolisms in response to environmental cues. In mammals, the regulatory subunits of mTORC1 include RAPTOR, which recruits mTORC1 substrates by interacting with their TOR signaling (TOS) motif. Despite the evolutionary conservation of mTORC1, no TOS motif has been described in lower eukaryotes. In addition, no apparent TOS motif is present in many of the known mTORC1 substrates, and very little is known about how mTORC1 recognizes substrates with no discernible TOS motif. Findings of this study have revealed that the mechanism of the TOS motif-mediated recruitment of the TORC1 substrates is conserved between fission yeast and humans.
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Free Research Field |
細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
mTORC1は、周辺環境の栄養源などに応答し、細胞成長や増殖を制御しているため、その活性異常はがんをはじめ、糖尿病や神経疾患など様々な疾病を原因となることがわかっている。また、近年mTORC1は老化や寿命と密接に関わることもわかってきており、医薬品開発における分子標的としてmTORC1が非常に注目されている。本研究は、mTORC1がどのようにして基質を認識するのかそのメカニズムを探るものであり、mTORC1シグナル経路の分子機構の理解のみならず、その臨床応用への足ががりとなる基盤情報の提供へとつながることが期待される。
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