Abnormalities of mitotic-kinase-mediated signal transduction and diseases

• Project/Area Number: 15K08324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Goto Hidemasa 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20393126)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 分裂期キナーゼ / Aurora-A / Plk1 / Ndel1 / 分裂間期 / 分裂期 / キナーゼ / 中心体 / がん / シリア病

Outline of Final Research Achievements

Aurora-A and Plk1 are known to be activated in mitosis. Recently, it was reported that these mitotic kinases also function in interphase. Abnormalities of these interphase functions are considered to be related to several diseases, such as cancer or ciliopathy, but the precise mechanisms remain unknown. In this research project, we found that Ndel1 functions upstream of Aurora-A in interphase. Since Ndel1-hypomorphoc mice exhibit ciliopathy-related disorders, these findings shed light on the pathogenesis of ciliopathy.

Research Products

• [Journal Article] Regulation of keratin 5/14 intermediate filaments by CDK1, Aurora-B, and Rho-kinase (2018)
  • Author(s): Inaba H, Yamakawa D, Tomono Y, Enomoto A, Mii S, Kasahara K, Goto H, Inagaki M
  • Journal Title: Biochem Biophys Res Commun Volume: 498 Issue: 3 Pages: 544-550
  • DOI: 10.1016/j.bbrc.2018.03.016
  • Peer Reviewed / Open Access
• [Journal Article] Mechanisms of ciliogenesis suppression in dividing cells. (2017)
  • Author(s): Goto H., Inaba H., and Inagaki M.
  • Journal Title: Cell. Mol. life Sci. Volume: 74 Issue: 5 Pages: 881-890
  • DOI: 10.1007/s00018-016-2369-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Desmin phosphorylation by Cdk1 is required for efficient separation of desmin intermediate filaments in mitosis and detected in murine embryonic/newborn muscle and human rhabdomyosarcoma tissues. (2016)
  • Author(s): Makihara H., Inaba H., Enomoto A., Tanaka H., Tomono Y., Ushida K., Goto M., Kurita K., Nishida Y., Kasahara K., Goto H., and Inagaki M.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 478 Issue: 3 Pages: 1323-1329
  • DOI: 10.1016/j.bbrc.2016.08.122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway. (2016)
  • Author(s): Inaba H, Goto H, Kasahara K, Kumamoto K, Yonemura S, Inoko A, Yamano S, Wanibuchi H, He D, Goshima N, Kiyono T, Hirotsune S, Inagaki M.
  • Journal Title: J Cell Biol. Volume: 212 Issue: 4 Pages: 409-423
  • DOI: 10.1083/jcb.201507046
  • Peer Reviewed / Open Access
• [Journal Article] Sphingolipids inhibit vimentin-dependent cell migration (2015)
  • Author(s): Hyder C.L., Kemppainen K., Isoniemi K.O., Imanishi S.Y., Goto H., Inagaki M., Fazeli E., Eriksson J.E., and Törnquist K.
  • Journal Title: J. Cell Sci. Volume: 128 Issue: 11 Pages: 2057-2069
  • DOI: 10.1242/jcs.160341
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytokinetic failure-induced tetraploidy develops into aneuploidy, triggering skin aging in phospho-vimentin deficient mice. (2015)
  • Author(s): Tanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., and Inagaki, M.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 21 Pages: 12984-12998
  • DOI: 10.1074/jbc.m114.633891
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Current topics of functional links between primary cilia and cell cycle (2015)
  • Author(s): Izawa I., Goto H., Kasahara K., and Inagaki M.
  • Journal Title: Cilia Volume: 4 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s13630-015-0021-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel Insights into Chk1 Regulation by Phosphorylation (2015)
  • Author(s): Goto, H., Kasahara, K., and Inagaki, M.
  • Journal Title: Cell Structure and Function Volume: 40 Issue: 1 Pages: 43-50
  • DOI: 10.1247/csf.14017
  • NAID: 130004885867
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Defect of Mitotic Vimentin Phosphorylation Causes Microophthalmia and Cataract via Aneuploidy and Senescence in Lens Epithelial Cells. (2016)
  • Author(s): Goto H. and Inagaki M.
  • Organizer: XXII Biennial Meeting of the International Society for Eye Research (ISER)
  • Place of Presentation: Keio Plaza Hotel (Tokyo)
  • Year and Date: 2016-09-28
  • Int'l Joint Research / Invited
• [Presentation] Ndel1は増殖細胞において一次線毛形成を抑制する (2016)
  • Author(s): 稲葉弘哲、後藤英仁、笠原広介、猪子誠人、熊本香奈子、米村重信、何東偉、五島直樹、山野荘太郎、鰐渕英機、広常真治、清野 透、稲垣 昌樹
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都テレサ（京都市）
  • Year and Date: 2016-06-16
• [Presentation] Vimentin phospho-deficient mice display aneuploidy and skin premature aging (2015)
  • Author(s): Tanaka H., Goto H., Inoko A., Makihara H., Enomoto A., Izawa I., and Inagaki M.
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-08
• [Book] Intermediate Filament Proteins, Vol 568, Methods in Enzymology (2016)
  • Author(s): Goto H., Tanaka H., Kasahara K., and Inagaki M.
  • Publisher: Academic Press (UK)
• [Remarks] 愛知県がんセンター研究所／部門紹介／腫瘍医化学部
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/08hatsugan_seigyo/index.html
• [Remarks] 腫瘍医化学部／部門紹介／愛知県がんセンター研究所
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/08hatsugan_seigyo/index.html