Signal cascades regulating cell cycle

• Project/Area Number: 17012012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: NISHIDA Eisuke Kyoto University, 大学院・生命科学研究科, 教授 (60143369)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥61,500,000 (Direct Cost: ¥61,500,000); Fiscal Year 2009: ¥12,300,000 (Direct Cost: ¥12,300,000); Fiscal Year 2008: ¥12,300,000 (Direct Cost: ¥12,300,000); Fiscal Year 2007: ¥12,300,000 (Direct Cost: ¥12,300,000); Fiscal Year 2006: ¥12,300,000 (Direct Cost: ¥12,300,000); Fiscal Year 2005: ¥12,300,000 (Direct Cost: ¥12,300,000)
• Keywords: MAPキナ-ゼ / ERK1 / 2 / G0 / G1期 / M期キナーゼ / Plk1 / Myt1 / 細胞分裂期 / 転写ネットワーク / MAPキナーゼ / Sprouty / E2F / Cdc2 / PI3キナーゼ / Akt / タイリングアレイ / BubR1

Research Abstract

We have identified two protein kinases, BubR1 and Myt1, as substrates of the M-phase protein kinase Plk1. Plk1 phosphorylation of BubR1 facilitated chromosome alignment during prometaphase while Myt1 was essential for Golgi and ER assembly during mitotic exit. We have also demonstrated that continuous ERK activation in response to growth factor stimulation downregulates antiproliferative genes throughout G1 phase to allow cell cycle progression.

Research Products

• [Journal Article] CrkL is a novel target of Sprouty2 in fibroblast growth factor signaling. (2010)
  • Author(s): Satoh, T., Torii. S., Nakayama, K., Nishida, E.
  • Journal Title: Genes Cells. 15 Pages: 161-168
  • Peer Reviewed
• [Journal Article] CrkL is a novel target of Sprouty2 in fibroblast growth factor signaling (2010)
  • Author(s): Satoh T., et al.
  • Journal Title: Genes Cells 15 Pages: 161-168
  • Peer Reviewed
• [Journal Article] Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transport. Nature Struct. (2009)
  • Author(s): Kosako, H., Yamaguchi, N., Aranami, C., Ushiyama, M., Kose, S., Imamoto, N., Taniguchi, H., Nishida, E., Hattori, S.
  • Journal Title: Mol. Biol. 16 Pages: 1026-1035
  • Peer Reviewed
• [Journal Article] Involvement of the protein kinase CK2 in the regulation of mammalian circadian rhythms. (2009)
  • Author(s): Tsuchiya, Y., Akashi, M., Matsuda, M., Goto, K., Miyata, Y., Node, K., Nishida, E.
  • Journal Title: Science Signaling 2
  • Peer Reviewed
• [Journal Article] Dual role of Cdc42 in spindle orientation control of adherent cells. (2009)
  • Author(s): Mitsushima, M., Toyoshima, F., Nishida, E.
  • Journal Title: Mol. Cell. Biol. 29 Pages: 2816-2827
  • Peer Reviewed
• [Journal Article] Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transport (2009)
  • Author(s): Kosako H., et al
  • Journal Title: Nat.Struct.Mol. Biol. 16 Pages: 1026-1035
  • Peer Reviewed
• [Journal Article] Dual role of Cdc42 in spindle orientation control of adherent cells (2009)
  • Author(s): Mitsushima M., et al.
  • Journal Title: Mol.Cell.Biol. 29 Pages: 2816-2827
  • Peer Reviewed
• [Journal Article] Downregulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signaling. (2008)
  • Author(s): Hayashi, H., Tsuchiya, Y., Nakayama, K., Satoh, T., Nishida, E.
  • Journal Title: Genes Cells 13 Pages: 941-947
  • Peer Reviewed
• [Journal Article] Ripples from neighbouring transcription. (2008)
  • Author(s): Ebisuya, M., Yamamoto, T., Nakajima, M., Nishida, E.
  • Journal Title: Nature Cell Biol. 10 Pages: 1106-1113
  • Peer Reviewed
• [Journal Article] FGF induces oscillations of Hes1 expression and Ras/ERK activation. (2008)
  • Author(s): Nakayama, K., Satoh, T., Igari, A., Kageyama, R., Nishida, E.
  • Journal Title: Curr. Biol. 18 Pages: 332-334
  • Peer Reviewed
• [Journal Article] Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit. (2008)
  • Author(s): Nakajima, H., Yonemura, S., Murata, M., Nakamura, N., Piwnica-Worms, H., Nishida, E.
  • Journal Title: J. Cell Biol. 181 Pages: 89-103
  • Peer Reviewed
• [Journal Article] Ripples from neighbouring transcription (2008)
  • Author(s): Ebisuya, M. et.al.
  • Journal Title: Nature Cell Biol 10 Pages: 1106-1112
  • Peer Reviewed
• [Journal Article] DoWn-regulation of the PI3-kinase/Akt pathway by ERK MAPkinase in growth factor signaling (2008)
  • Author(s): Hayashi, H. et.al.
  • Journal Title: Genes Cells 13 Pages: 941-947
  • Peer Reviewed
• [Journal Article] Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit. (2008)
  • Author(s): Nakajima, H., et. al.
  • Journal Title: J. Cell Biol. 181 Pages: 89-103
  • Peer Reviewed
• [Journal Article] Activation of a C-terminal transcriptional activation domain of ERK5 by autophsophorylation. (2007)
  • Author(s): Morimoto, H., Kondoh, K., Nishimoto, S., Terasawa, K., Nishida, E.
  • Journal Title: J. Biol. Chem. 282 Pages: 35449-35456
  • Peer Reviewed
• [Journal Article] PtdIns(3, 4, 5)P3 Regulates Spindle Orientation in Adherent Cells. (2007)
  • Author(s): Toyoshima, F., Matsumura, S., Morimoto, H., Mitsushima, M., Nishida, E.
  • Journal Title: Dev. Cell 1 Pages: 796-811
  • Peer Reviewed
• [Journal Article] Plk1 facilitates chromosome alignment during prometaphase through BubR1. (2007)
  • Author(s): Matsumura, S., Toyoshima, F., Nishida, E.
  • Journal Title: J. Biol. Chem. 282 Pages: 15217-15227
  • Peer Reviewed
• [Journal Article] Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. (2007)
  • Author(s): Toyoshima, F., Nishida, E.
  • Journal Title: EMBO J. 26 Pages: 1487-1498
  • Peer Reviewed
• [Journal Article] Purification of phosphoproteins by immobilized metal affinity chromatography and its application to phosphoproteome analysis. (2007)
  • Author(s): Machida, M., Kosako, H., Shirakabe, K., Kobayashi, M., Ushiyama, M., Inagawa, J., Hirano, J., Nakano, T., Bando, Y., Nishida, E., Hattori, S.
  • Journal Title: FEBS J. 274 Pages: 1576-1587
  • Peer Reviewed
• [Journal Article] Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis. (2007)
  • Author(s): Kondoh, K., Sunadome, K., Nishida, E.
  • Journal Title: J. Biol. Chem. 282 Pages: 3058-3065
  • Peer Reviewed
• [Journal Article] PtdIns (3,4,5)P3 regulates spindle orientation in adherent cells. (2007)
  • Author(s): Toyoshima, F., et. al.
  • Journal Title: Dev. Cell 13 Pages: 796-811
  • Peer Reviewed
• [Journal Article] Activation of a C-terminal transcriptional activation domain of ERK5 by autophosphorylation. (2007)
  • Author(s): Morimoto, H., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 35449-35456
  • Peer Reviewed
• [Journal Article] Plk1 facilitates chromosome alignment during prometaphase through BubR1. (2007)
  • Author(s): Matumura, S.et al.
  • Journal Title: J.Biol.Chem. (in press)
• [Journal Article] MAPK signalling: ERK5 versus ERK1/2. (2006)
  • Author(s): Nishimoto, S., Nishida, E.
  • Journal Title: EMBO Rep. 7 Pages: 782-786
  • Peer Reviewed
• [Journal Article] Continuous ERK Activation Downregulates Antiproliferative Genes throughout G1 Phase to Allow Cell-Cycle Progression. (2006)
  • Author(s): Yamamoto, T., Ebisuya, M., Ashida, F., Okamoto, K., Yonehara, S., Nishida, E.
  • Journal Title: Curr. Biol. 16 Pages: 1171-1182
  • Peer Reviewed
• [Journal Article] Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms. (2006)
  • Author(s): Kondoh, K., Terasawa, K., Morimoto, H., Nishida, E.
  • Journal Title: Mol. Cell. Biol. 26 Pages: 1679-1690
  • Peer Reviewed
• [Journal Article] Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. (2006)
  • Author(s): Fujioka, A., Terai, K., Itoh, R.E., Aoki, K., Nakamura, T., Kuroda, S., Nishida, E., Matsuda, M.
  • Journal Title: J. Biol. Chem. 281 Pages: 8917-8926
  • Peer Reviewed
• [Journal Article] Centaurin-alpha1 is a phosphatidylinositol 3- kinase-dependent activator of ERK1/2 mitogen-activated protein kinases. (2006)
  • Author(s): Hayashi, H., Matsuzaki, O., Muramatsu, S., Tsuchiya, Y., Harada, T., Suzuki, Y., Sugano, S., Matsuda, A., Nishida, E.
  • Journal Title: J. Biol. Chem. 281 Pages: 1332-1337
  • Peer Reviewed
• [Journal Article] Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. (2006)
  • Author(s): Yamamoto, T.et al.
  • Journal Title: Curr.Biol. 16 Pages: 1171-1182
• [Journal Article] XGAP, an ArfGAP, is required for polarized localization of PAR proteins and cell polarity in Xenopus gastrulation. (2006)
  • Author(s): Hyodo-Miura, J.et al.
  • Journal Title: Dev.Cell 11 Pages: 69-79
• [Journal Article] ERK MAP kinase in G1 cell cycle progression and cancer. (2006)
  • Author(s): Torii, S.et al.
  • Journal Title: Cancer Sci. 97 Pages: 697-702
• [Journal Article] MAPK signalling : ERK5 versus ERK1/2. (2006)
  • Author(s): Nishimoto, S., Nishida, E.
  • Journal Title: EMBO Rep. 7 Pages: 782-786
• [Journal Article] Centaurin-alpha1 is a phosphatidylinositol 3-kinase-dependent activator of ERK1/2 mitogen-activated protein (2006)
  • Author(s): Hayashi, H. et al.
  • Journal Title: J.Biol.Chem. 281 Pages: 1332-1337
• [Journal Article] Dynamics of the RAS/ERK map kinase cascade as monitored by fluorescence probes. (2006)
  • Author(s): Fujioka, A. et al.
  • Journal Title: J.Biol.Chem. 281 Pages: 8917-8926
• [Journal Article] Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and (2006)
  • Author(s): Kondoh, K. et al.
  • Journal Title: Mol.Cell.Biol. 26 Pages: 1679-1690
• [Journal Article] The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. (2005)
  • Author(s): Ebisuya, M., Kondoh, K., Nishida, E.
  • Journal Title: J. Cell Sci. 118 Pages: 2997-3002
  • Peer Reviewed
• [Journal Article] The duration, magnitude and compartmentalization of ERK MAP kinase activity : mechanisms for providing signaling (2005)
  • Author(s): Ebisuya, M. et al.
  • Journal Title: J.Cell Sci. 118 Pages: 2997-3002
• [Journal Article] Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development. (2005)
  • Author(s): Nishimoto, S. et al.
  • Journal Title: EMBO Rep. 6 Pages: 1064-1069
• [Journal Article] The C.elegans p38 MAPK pathway.regulates nuclear localization of the transcription factor SKN-1 in (2005)
  • Author(s): Inoue, H. et al.
  • Journal Title: Genes Dev. 19 Pages: 2278-2283
• [Presentation] MAP kinase signaling: Regulatory mechanisms and functions. (2010)
  • Author(s): Nishida, E.
  • Organizer: International Conference on Radiation and Cancer Biology
  • Place of Presentation: Nagasaki University, Nagasaki, Japan
• [Presentation] ERK MAP kinase signaling: Regulatory mechganisms and function. (2009)
  • Author(s): Nishida, E.
  • Organizer: International Symposium on Frontiers of Protein Science
  • Place of Presentation: Senri Hankyu Hotel, Osaka, Japan
  • Year and Date: 2009-11-14
• [Presentation] 細胞分裂期におけるアクチンダイナミクス (2009)
  • Author(s): 満島勝, ら
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] FGF経路におけるSproutyの新規標的因子CrkLの同定 (2009)
  • Author(s): 佐藤崇之, ら
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] ERK MAP kinase signaling: Regulatory mechganisms and function. (2008)
  • Author(s): Nishida, E.
  • Organizer: 8th International Conference on Protein Phosphatases
  • Place of Presentation: Maebashi TERRSA, Gunma, Japan
• [Presentation] Ripples from neighboring transcription (2008)
  • Author(s): Ebisuya, M., Yamamoto, T., Nakajima, M., Nishida, E.
  • Organizer: The 6th International Student Seminar
  • Place of Presentation: Shiran Kaikan, Kyoto University, Kyoto, Japan
• [Presentation] Dual role of Cdc42 in the spindle orientation control inadherent cell (2008)
  • Author(s): Mitsushima, M. et.al.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Cdc42 and PAK2 Control the Mitotic Spindle Orientation in Mammalian Cells. (2007)
  • Author(s): Mitsushima, M., Toyoshima, F., Nishida, E.
  • Organizer: The 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington Convention Center, Washington DC, USA
• [Presentation] Antagonistic Interactions between the Retinoic Acid Receptor and Ras/ERK Signaling Pathways in Colorectal Cancer Cells. (2007)
  • Author(s): Imajo, M., Kondoh, K., Yamamoto, T., Nakayama, K., Nishida, E.
  • Organizer: The 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington Convention Center, Washington DC, USA
• [Presentation] Ripples from neighboring transcription. (2007)
  • Author(s): Ebisuya, M., Yamamoto, T., Nishida, E.
  • Organizer: The 7th International Workshop on Advanced Genomics
  • Place of Presentation: Tokyo International Forum, Tokyo, Japan
• [Presentation] Ripples from neighboring transcription (2007)
  • Author(s): Ebisuya, M., et. al.
  • Organizer: The 7th International Workshop on Advanced Genomics
  • Place of Presentation: Tokyo International Forum, Tokyo, Japan
• [Presentation] Regulation of nuclear translocation of ERK5" Kyoto University 21st Century COE program "COE Formation in Frontier Life Science by Unifying Interactions (2006)
  • Author(s): Kondoh, K., Terasawa, K., Morimoto, H., Nishida, E.
  • Organizer: The 4th International Student Seminar
  • Place of Presentation: Kyoudai-Kaikan, Kyoto, Japan
• [Presentation] Signal transduction by the ERK family of MAP kinases. (2006)
  • Author(s): Nishida, E.
  • Organizer: International Symposium of Kobe University 21st COE Program on Signal Transduction
  • Place of Presentation: Kobe, Japan
• [Presentation] M phase protein kinases and their function. (2005)
  • Author(s): Nishida, E.
  • Organizer: International Symposium on Ran and Cell Cycle
  • Place of Presentation: Awaji, Japan
• [Presentation] FGF signaling regulates the oscillatory expression of Hes1 in cultured cells (2005)
  • Author(s): Nakayama, K., Kondoh, K., Kageyama, R., Nishida, E.
  • Organizer: he 15th International Society of Developmental Biologists Congress
  • Place of Presentation: Sydney, Australia