Elucidation of new functions of intermediate filaments linking a relationship between proliferation and differentiation

2013 Fiscal Year Final Research Report

• Project/Area Number: 23247035
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: INAGAKI Masaki 愛知県がんセンター(研究所), 腫瘍医化学部, 部長 (30183007)
• Co-Investigator(Kenkyū-buntansha): IZAWA Ichiro 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20311441) ; GOTO Hidemasa 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20393126) ; KASAHARA Kousuke 愛知県がんセンター(研究所), 腫瘍医化学部, 研究員 (90455535)
• Project Period (FY): 2011-11-18 – 2014-03-31
• Keywords: 中間径フィラメント / 増殖 / 分化 / ケラチン / 細胞骨格 / 中心体

Research Abstract

To uncover roles of intermediate filaments in proliferation and differentiation, we studied the functions of trichoplein, a keratin-binding protein, and trichoplein-related proteins. We found that trichoplein-Aurora-A pathway is required for G1 progression through a key role in the continuous suppression of primary cilia assembly. On the other hand, we revealed that knock-in mice expressing phosphodeficient vimentin variants developed binucleation and aneuploidy in lens epithelial cells, which promoted lens cataract, an aging phenotype.

Research Products

• [Journal Article] New insights into roles of intermediate filament phosphorylation and progeria pathogenesis (2014)
  • Author(s): Goto, H., and Inagaki, M.
  • Journal Title: IUBMB Life Volume: 66 Pages: 195-200
• [Journal Article] Cdk1 Coordinates Timely Activation of MKlp2 Kinesin with Relocation of the Chromosome Passenger Complex for Cytokinesis (2014)
  • Author(s): Kitagawa, M., Fung, S.Y.S., Hameed, U.F.S., Goto, H., Inagaki, M., Lee, S.H.
  • Journal Title: Cell Rep. Volume: 7 Pages: 166-179
• [Journal Article] Inhibition of endocytic vesicle fusion by Plk1-mediated phosphorylation of vimentin during mitosis (2014)
  • Author(s): Ikawa, K., Satou, A., Fukuhara, M., Matsumura, S., Sugiyama, N., Goto, H., Fukuda, M., Inagaki, M., Ishihama, Y. and Toyoshima, F.
  • Journal Title: Cell Cycle Volume: 13 Pages: 126-137
• [Journal Article] Defect of mitotic vimentin phosphorylation causes microophthalmia and cataract via aneuploidy and senescence in lens epithelial cells (2013)
  • Author(s): Matsuyama, M., Tanaka, H., Inoko, A., Goto, H., Yonemura, S., Kobori, K., Hayashi, Y., Kondo, E., Itohara, S., Izawa, I. and Inagaki, M.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 35626-35635
• [Journal Article] PI 3-kinase-dependent phosphorylation of Plk1-Ser99 promotes association with 14-3-3γ and is required for metaphase-anaphase transition (2013)
  • Author(s): Kasahara, K., Goto, H., Izawa, I., Kiyono, T., Watanabe, N., Elowe, S., Nigg, E.A. and Inagaki, M.
  • Journal Title: Nat. Commun. Volume: 4 Pages: 1882
  • DOI: 10.1038/ncomms2879
• [Journal Article] Cell cycle progression by the repression of primary cilia formation in proliferating cells (2013)
  • Author(s): Goto, H., Inoko, A. and Inagaki, M.
  • Journal Title: Cell. Mol. Life Sci. Volume: 70 Pages: 3893-3905
• [Journal Article] The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK-and p53-independent accumulation of p21WAF1/CIP1 (2013)
  • Author(s): Neise, D., Sohn, D., Stefanski, A., Goto, H., Inagaki, M., Wesselborg, S., Budach, W., Stuhler, K. and Janicke, R.U.
  • Journal Title: Cell Death and Dis. Volume: 4 Pages: e859
• [Journal Article] Keratin 8 Is Required for the Maintenance of Architectural Structure in Thymus Epithelium (2013)
  • Author(s): Odaka, C., Loranger, A., Takizawa, K., Ouellet, M., Tremblay, M.J., Murata, S., Inoko, A., Inagaki, M. and Marceau, N.
  • Journal Title: PLoS ONE Volume: 8 Pages: e75101
• [Journal Article] Detection of vimentin serine phosphorylation by multicolor Quenchbodies (2013)
  • Author(s): Jeong, H.J., Ohmuro-Matsuyama, Y., Ohashi, H., Ohsawa, F., Tatsu, Y., Inagaki, M. and Ueda, H.
  • Journal Title: Biosens Bioelectron Volume: 40 Pages: 17-23
• [Journal Article] Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells (2012)
  • Author(s): Inoko, A., Matsuyama, M., Goto, H., Ohmuro-Matsuyama, Y., Hayashi, Y., Enomoto, M., Ibi, M., Urano, T., Yonemura, S., Kiyono, T., Izawa, I. and Inagaki, M.
  • Journal Title: J. Cell Biol. Volume: 197 Pages: 391-405
• [Journal Article] P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation (2012)
  • Author(s): Li, P., Goto, H., Kasahara, K., Matsuyama, M., Wang, Z., Yatabe, Y., Kiyono, T. and Inagaki, M.
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 1582-1592
• [Journal Article] Evidence that formation of Vimentin/Mitogen-activated Protein Kinase (MAPK) complex mediates mast cell activation following FcεRI/CC chemokine receptor 1 cross-talk (2012)
  • Author(s): Toda, M., Kuo, C.H., Borman, S.K., Richardson, R.M., Inoko, A., Inagaki, M., Collins, A., Schneider, K. and Ono, S.J.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 24516-24524
• [Presentation] Emerging role of the ubiquitin-proteasome pathway in primary cilia assembly (2013)
  • Author(s): Inagaki, M
  • Organizer: The 25th CDB meeting "Cilia and centrosomes, from fertilization to cancer"
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20130617-18
• [Presentation] 細胞質分裂障害は染色体不安定性の亢進および細胞老化を誘導する (2013)
  • Author(s): 田中宏樹
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-06-21
• [Presentation] Screening of novel Aurora-A-associated proteins to prevent primary cilia assembly at the centrosome in proliferating cells (2013)
  • Author(s): Goto, H
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-06-20
• [Presentation] Translocation of keratin-binding proteins between the cell-cell adhesion and the centrosome as the functional switch of differentiation and proliferation (2013)
  • Author(s): Inoko, A
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-06-19
• [Presentation] ビメンチンリン酸化の生理学的意義の解明 (2013)
  • Author(s): 稲垣昌樹
  • Organizer: 第13回日本蛋白質科学学会年会
  • Place of Presentation: 鳥取
  • Year and Date: 2013-06-12
• [Presentation] Intermediate filaments and site-and phosphorylation state-specific antibodies (2012)
  • Author(s): Inagaki, M
  • Organizer: Global COE the 4th International Symposium
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2012-11-15
• [Presentation] Intermediate filaments and site-and phosphorylation state-specific antibodies (2012)
  • Author(s): Inagaki, M
  • Organizer: Lecture at The University of Gothenburg
  • Place of Presentation: Gothenberg, Sweden
  • Year and Date: 2012-09-24
• [Book] Method for generation of antibodies specific for site-and post-translational modifications. Ossipow V. and Fischer N. (eds.), Monoclonal Antibodies: Methods and Protocols, Methods in Molecular Biology, vol. 1131 (2014)
  • Author(s): Goto, H. and Inagaki, M.
  • Publisher: Springer Science+Business Media New York(in press)
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center