Signal transduction networks regulating life span and development

• Project/Area Number: 16GS0310
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• 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): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥658,450,000 (Direct Cost: ¥506,500,000、Indirect Cost: ¥151,950,000); Fiscal Year 2008: ¥136,500,000 (Direct Cost: ¥105,000,000、Indirect Cost: ¥31,500,000); Fiscal Year 2007: ¥136,500,000 (Direct Cost: ¥105,000,000、Indirect Cost: ¥31,500,000); Fiscal Year 2006: ¥134,290,000 (Direct Cost: ¥103,300,000、Indirect Cost: ¥30,990,000); Fiscal Year 2005: ¥128,830,000 (Direct Cost: ¥99,100,000、Indirect Cost: ¥29,730,000); Fiscal Year 2004: ¥122,330,000 (Direct Cost: ¥94,100,000、Indirect Cost: ¥28,230,000)
• Keywords: シグナル伝達 / 寿命 / 発生 / 老化 / 食餌制限 / 断続的飢餓 / カロリー制限 / Rheb / 初期胚発生 / Wnt経路 / DAF16 / MAPキナーゼ / Wnt / 着床前発生 / DAF-16 / 神経分化 / ERK5 / インスリン様経路 / daf-16 / bml-1 / 神経発生 / 線虫 / インスリン経路

Research Abstract

線虫において断続的飢餓が著しく寿命を促進し、Rheb 経路がその寿命促進に必要であることを発見した。脊椎動物初期胚発生過程の背腹軸決定において、フィードバックインヒビターSprouty によるERK 経路の活性化時間の制御が必須であることを発見した。ERK の核内での作用機構について解析し、ERK 依存的な遺伝子の転写促進が起こる場合に、その遺伝子の近傍領域の転写も活性化する「転写の波及効果」を発見した。

Research Products

• [Journal Article] Signalling through Rheb mediates intermittent fasting-induced longevityin C. (2009)
  • Author(s): Honjoh, S., Yamamoto, T., Uno, M. and Nishida, E.
  • Journal Title: elegans. Nature 457 Pages: 726-730
• [Journal Article] Regulation of the ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • Author(s): Hanafusa, H., Matsumoto, K. and Nishida, E.
  • Journal Title: Nature Cell Biol 11 Pages: 106-109
• [Journal Article] Singmalling through RHEB-1 mediates intermittent fasting-induced lingevity in C. elegans (2009)
  • Author(s): Honjoh, S., et al.
  • Journal Title: Nature 457 Pages: 726-730
  • Peer Reviewed
• [Journal Article] Regulation of ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • Author(s): Hanafusa, H., et al.
  • Journal Title: Nature Cell Biol. 11 Pages: 106-109
  • Peer Reviewed
• [Journal Article] Ripples from neighbouring transcription (2008)
  • Author(s): Ebisuya, M., Yamamoto, T., Nakajima, M. and Nishida, E.
  • Journal Title: Nature Cell Biol 10 Pages: 1106-1113
• [Journal Article] FGF induces oscillations of Hes1 expression and Ras/ERK activation (2008)
  • Author(s): Nakayama, K., Satoh, T., Igari, A., Kageyama, R. and Nishida, E.
  • Journal Title: Curr. Biol 18
• [Journal Article] Myt1 protein kinase is essential for Golgi and ER assenmbly during mitotic exit (2008)
  • Author(s): Nakajima, H., Yonemura, S., Murata, M., Nakamura, N., Piwnica-Worms, H. and Nishida, E.
  • Journal Title: J. Cell Biol 181 Pages: 89-103
• [Journal Article] FGF induces oscillations of Hes1 expression and Ras/ERK activation. (2008)
  • Author(s): Nakayama, K., et. al.
  • Journal Title: Curr. Biol. (in press)
  • 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. and Nishida, E.
  • Journal Title: Dev. Cell 13 Pages: 796-811
• [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., and Nishida, E.
  • Journal Title: EMBO J 26 Pages: 1487-1498
• [Journal Article] Wntll stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through (2007)
  • Author(s): Yamanaka, H., and Nishida, E.
  • Journal Title: Genes Cells 12 Pages: 961-967
  • Peer Reviewed
• [Journal Article] Requirement for ERK MAP kinase in mouse preimplantation development. (2007)
  • Author(s): Maekawa, M., et. al.
  • Journal Title: Development 134 Pages: 2751-2759
  • Peer Reviewed
• [Journal Article] Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis. (2007)
  • Author(s): Kondoh, K. et al.
  • Journal Title: J.Biol.Chem. 282 Pages: 3058-3065
• [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
• [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. and Nishida, E.
  • Journal Title: Curr. Biol 16 Pages: 1171-1182
• [Journal Article] MAPK signalling : ERK5 versus ERK1/2 (2006)
  • Author(s): Nishimoto, S. and Nishida, E.
  • Journal Title: EMBO Rep 7 Pages: 782-786
• [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] 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. 12 Pages: 1171-1182
• [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] Regulatory mechanisms and functions of MAP kinase signaling pathways. (2006)
  • Author(s): Imajo, M. et al.
  • Journal Title: IUBMB Life 58 Pages: 312-317
• [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] Requirement of the MAP kinase signaling pathways for mouse preimplantation development (2005)
  • Author(s): Maekawa, M., Yamamoto, T., Tanoue, T., Yuasa, Y., Chisaka, O. and Nishida, E.
  • Journal Title: Development 132 Pages: 1173-1783
• [Journal Article] Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development (2005)
  • Author(s): Nishimoto, S., Kusakabe, M. and Nishida, E.
  • Journal Title: EMBO Rep 6 Pages: 1064-1069
• [Journal Article] Resetting of peripheral circadian clock by prostaglandin E2. (2005)
  • Author(s): Tsuchiya, Y. et al.
  • Journal Title: EMBO Rep. 6 Pages: 256-261
• [Journal Article] Xenopus ILK (integrin-linked kinase) is required for morphogenetic movements during gastrulation. (2005)
  • Author(s): Yasunaga, T. et al.
  • Journal Title: Genes Cells 10 Pages: 369-379
• [Journal Article] Requirement of the MAP kinase signaling pathways for mouse preimplantation development. (2005)
  • Author(s): Maekawa, M. et al.
  • Journal Title: Development 132 Pages: 1173-1783
• [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
• [Journal Article] Requirement of the MAP kinase signaling pathways for mouse preimplantation development. (2005)
  • Author(s): Maekawa, M. et al.
  • Journal Title: Development (In press)
• [Journal Article] The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC (2004)
  • Author(s): Kusakabe, M. and Nishida, E.
  • Journal Title: EMBO J 23 Pages: 4190-4201
• [Journal Article] Sef is a spatial regulator for Ras/MAP kinase signaling (2004)
  • Author(s): Torii, S., Kusakabe, M., Yamamoto, T., Maekawa, M. and Nishida, E.
  • Journal Title: Dev. Cell 7 Pages: 33-44
• [Journal Article] ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing (2004)
  • Author(s): Matsubayashi, Y., Ebisuya, M., Honjoh, S. and Nishida, E.
  • Journal Title: Curr. Biol 14 Pages: 731-735
• [Journal Article] Sef is a spatial regulator for Ras/MAP kinase signaling. (2004)
  • Author(s): Torii, S. et al.
  • Journal Title: Dev.Cell 7 Pages: 33-44
• [Journal Article] Shp2, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. (2004)
  • Author(s): Hanafusa, H. et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 22992-22995
• [Journal Article] The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC. (2004)
  • Author(s): Kusakabe, M. et al.
  • Journal Title: EMBO J. 23 Pages: 4190-4201
• [Presentation] Serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes cell survival by suppressing the expression of death-inducing signaling complex (DISC) components in early Xenopus development (2008)
  • Author(s): Endo, T., Kusakabe, M., Sunadome, K., Yamamoto, T. and Nishida, E.
  • Organizer: The 12th International Xenopus conference
  • Place of Presentation: Eurostrand Hotel, Leiwen, Germany
• [Presentation] Functional analysis of EIG121L (estrogen induced gene 121-like) in early Xenopus development (2008)
  • Author(s): Araki, T., Kusakabe, M. and Nishida, E.
  • Organizer: The 12th International Xenopus Conference
  • Place of Presentation: Eurostrand Hotel, Leiwen, Germany
• [Presentation] Functional analysis of EIG121L in early Xenopus development (2008)
  • Author(s): Araki, T., et al.
  • Organizer: The 12th International Xenopus Conference
  • Place of Presentation: Leiwen, Germany
• [Presentation] Rheb is required for intermittent fasting-induced lifespan extension. (2007)
  • Author(s): Honjoh, S., and Nishida, E.
  • Organizer: 16th International C. elegans meeting
  • Place of Presentation: University of California
  • Year and Date: 2007-06-07
• [Presentation] Rheb is required for intermittent fasting-induced life span extension (2007)
  • Author(s): Honjoh, S. and Nishida, E.
  • Organizer: 16th International C
  • Place of Presentation: elegans meeting University of California
• [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. and Nishida, E.
  • Organizer: The 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington Convention Center, Washington DC, USA
• [Presentation] A screen for genes comprising C. elegans MAPK cascades that affect the lifespan (2006)
  • Author(s): Okuyama, T., Kano, K., Ookuma, S., Inoue, H., Hisamoto, N., Matsumoto, K. and Nishida, E.
  • Organizer: The 2nd East Asia C. elegans Meeting
  • Place of Presentation: The Hoam Convention Center, Seoul National University, Seoul, Korea
• [Presentation] Signal transduction by the ERK family of MAP kinases (2006)
  • Author(s): Nishida, E
  • Organizer: International Symposium of Kobe University 21st century COE program on Signal transduction In Memory of Prof. Yasutomi Nishizuka
  • Place of Presentation: International Conference Center Kobe, Japan
• [Presentation] The MEK5-ERK5 pathway is essential for Xenopus neural differentiation (2005)
  • Author(s): Nishimoto, S., Kusakabe, M. and Nishida, E.
  • Organizer: 15th International Society of Developmental Biologists Congress 2005
  • Place of Presentation: Sydney, Australia
• [Presentation] Extension of the lifespan of Caenorhabditis elegans by beta-the lifespan of Caenorhabditis elegans by betacarotene (2005)
  • Author(s): Ookuma, S., Taniguchi, E., Bamba, C., Kanoh, K., Hashimoto, Y. and Nishida, E
  • Organizer: 15th International C. elegans Conference
  • Place of Presentation: University of California, Los Angeles, California, USA
• [Presentation] Signal transduction by the ERK family of MAP kinases (2004)
  • Author(s): Nishida, E
  • Organizer: The First Shanghai Symposium On Signal Transduction And Cancer
  • Place of Presentation: Shanghai, China