Reguratory mechanism of TOR Complex 2 on glucose stimuli

• Project/Area Number: 25440086
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: 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)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: TOR / Target Of Rapamycin / グルコース / 分裂酵母 / Rab低分子量Gタンパク質

Outline of Final Research Achievements

The TORC2 - Akt pathway is evolutionarily conserved from yeast to human. Whereas the human TORC2 pathway responds to insulin stimuli, the TORC2 pathway in a unicellular organism fission yeast directly responds to glucose in the extracellular environment. In the previous study, we utilized fission yeast as a model organism and found that Ryh1, a known activator of TORC2, is involved in glucose response of fission yeast TORC2.
In this study, we have discovered a novel mechanism that regulates TORC2 on glucose stimuli independently of Ryh1, although the precise molecular mechanism has remained to be elucidated. We have also revealed a key molecular mechanism how TORC2 activates Akt.

Research Products

• [Journal Article] Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit (2017)
  • Author(s): Hisashi Tatebe, Shinichi Murayama, Toshiya Yonekura, Tomoyuki Hatano, David Richter, Tomomi Furuya, Saori Kataoka, Kyoko Furuita, Chojiro Kojima, and Kazuhiro Shiozaki
  • Journal Title: eLife Volume: 6
  • DOI: 10.7554/elife.19594
  • NAID: 120005983409
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose (2015)
  • Author(s): Tomoyuki Hatano, Susumu Morigasaki, Hisashi Tatebe, Kyoko Ikeda, Kazuhiro Shiozaki
  • Journal Title: Cell Cycle Volume: 14 Issue: 6 Pages: 848-856
  • DOI: 10.1080/15384101.2014.1000215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclodextrin Complexed [60]Fullerene Derivatives with High Levels of Photodynamic Activity by Long Wavelength Excitation. (2013)
  • Author(s): Ikeda A, Iizuka T, Maekubo N, Aono R, Kikuchi J, Akiyama M, Konishi T, Ogawa T, Ishida-Kitagawa N, Tatebe H, Shiozaki K
  • Journal Title: ACS Medicinal Chemistry Letters Volume: 4 Issue: 8 Pages: 752-756
  • DOI: 10.1021/ml4001535
  • Peer Reviewed
• [Presentation] Regulation of TOR Complex 2 (TORC2) and its physiological roles in response to the extracellular environment (2014)
  • Author(s): Hisashi Tatebe, Tomoyuki Hatano, Susumu Morigasaki, Midori Emori, Kazuhiro Shiozaki
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Role of Sin1 in TORC2 signaling (2013)
  • Author(s): Hisashi Tatebe
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Invited
• [Remarks] ガン増殖を引き起こすタンパク質Sin1 の構造を明らかに｜奈良先端科学技術大学院大学
  • URL: http://www.naist.jp/news/2017/03/003680.html
• [Remarks] Yeast enzyme regulator recognized
  • URL: http://ipw.naist.jp/iri/naura/RH_pdf/NAIST_RH-24_BS_19.pdf