Regulation of cell polarity by proto-oncogene Akt

• Project/Area Number: 15K06990
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Rikkyo University (2017-2018); The University of Tokyo (2015-2016)
• Principal Investigator: HIGUCHI Maiko 立教大学, 理学部, 助教 (30420235)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Akt / 微小管 / 細胞極性 / 細胞運動 / PI3K

Outline of Final Research Achievements

Directed cell migration is important for various cellular processes including immune response, tissue development and tissue repair. However, the underlying mechanisms are still not fully understood. In this study, we examined the roles of the PI3K-Akt pathway in the regulation of microtubule dynamics and found Akt1 can phosphorylate EB2/RP1, a member of EB family microtubule associated proteins. We are now trying to understand the molecular mechanisms by which EB2/RP1 regulates microtubule dynamics and the relationships between Akt1 and EB2/RP1.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、細胞外の環境に応じて細胞が運動方向を決定する、という細胞にとって非常に重要な機構の解明に貢献することが出来た。さらに、Aktの異常な活性化は癌悪性化と関連が深いため、本研究の成果はAkt依存的な癌悪性化を制圧するための薬剤ターゲットの提供にもつながると考えている。

Research Products

• [Journal Article] The PDK1-Akt Pathway Regulates Radial Neuronal Migration and Microtubules in the Developing Mouse Neocortex (2016)
  • Author(s): Itoh, Y., Higuchi, M., Oishi, K.,Kishi, Y., Okazaki, T., Sakai, H., Miyata, T., Nakajima, K., Gotoh, Y.
  • Journal Title: PNAS. Volume: 113(21) Issue: 21 Pages: 2955-64
  • DOI: 10.1073/pnas.1516321113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response. (2015)
  • Author(s): Okazaki T., Higuchi M., Takeda K., Iwatsuki-Horimoto K., Kiso M., Miyagishi M., Yanai H., Kato A., Yoneyama M., Fujita T., Taniguchi T., Kawaoka Y., Ichijo H. and Gotoh Y.
  • Journal Title: Science Signaling Volume: 8 Issue: 388 Pages: 1-12
  • DOI: 10.1126/scisignal.aab1883
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Novel mechanism of regulation of microtubule dynamics by EB2/RP1 microtubule binding protein (2018)
  • Author(s): 樋口麻衣子、大西啓介、後藤由季子
  • Organizer: 日本細胞生物学会
• [Presentation] 微小管結合分子EB2/RP1による微小管動態制御 (2017)
  • Author(s): 樋口麻衣子、大西啓介、久保田紘史、後藤由季子
  • Organizer: 日本細胞生物学会
  • Invited
• [Presentation] 原癌遺伝子Aktによる上皮細胞間接着の制御機構の解明 (2017)
  • Author(s): 西春佳、カン洪月、西川紗織、後藤由季子、樋口麻衣子
  • Organizer: 日本分子生物学会
• [Presentation] 原癌遺伝子AktによるE-カドヘリンを介した細胞間接着制御メカニズムの解明 (2015)
  • Author(s): カン洪月、西川沙織、後藤由季子、樋口麻衣子
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Book] 生体の科学 66(5) (2015)
  • Author(s): 樋口麻衣子
  • Total Pages: 2
  • Publisher: 医学書院