TOR kinase complexes that sense and integrate major nutritional signals

2017 Fiscal Year Final Research Report

• Project/Area Number: 26291024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Shiozaki Kazuhiro 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (00610015)
• Co-Investigator(Renkei-kenkyūsha): TATEBE Hisashi 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (00596819) ; FUKUDA Tomoyuki 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (90415282) ; KOJIMA Chojiro 大阪大学, たんぱく質研究所, 准教授 (50333563)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: TOR / 分裂酵母 / 栄養源 / 細胞増殖

Outline of Final Research Achievements

TOR protein kinase forms two distinct complexes, called TOR complex 1 (TORC1) and TOR complex 2 (TORC2), both of which are implicated in cancerous cell proliferation and metabolic syndrome. By using fission yeast as a genetically amenable model system, we have demonstrated that a Rab-family GTPase activates TORC2 in response to extracellular glucose. Within TORC2, we have found that the Sin1 subunit is responsible for binding the TORC2 substrates. The TORC2 substrates interact with the Sin1 CRIM domain, whose NMR structure has a ubiquitin-like fold with a characteristic acidic loop. Lastly, we have shown that the Rag-family GTPase heterodimer Gtr1-Gtr2 at vacuolar membranes plays an important role in suppressing TORC1 activity. This negative regulation of TORC1 requires the GATOR1 complex that functions as GTPase-Activating Protein (GAP) for the Gtr1 GTPase.

Free Research Field

細胞生物学