寿命と発生を制御するシグナル伝達ネットワーク

• 研究課題/領域番号: 16GS0310
• 研究種目: 学術創成研究費
• 配分区分: 補助金
• 研究機関: 京都大学
• 研究代表者: 西田 栄介 京都大学, 大学院・生命科学研究科, 教授 (60143369)
• 研究期間 (年度): 2004 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 658,450千円 (直接経費: 506,500千円、間接経費: 151,950千円); 2008年度: 136,500千円 (直接経費: 105,000千円、間接経費: 31,500千円); 2007年度: 136,500千円 (直接経費: 105,000千円、間接経費: 31,500千円); 2006年度: 134,290千円 (直接経費: 103,300千円、間接経費: 30,990千円); 2005年度: 128,830千円 (直接経費: 99,100千円、間接経費: 29,730千円); 2004年度: 122,330千円 (直接経費: 94,100千円、間接経費: 28,230千円)
• キーワード: 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

研究概要

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。

研究成果

• [雑誌論文] Signalling through Rheb mediates intermittent fasting-induced longevityin C. (2009)
  • 著者名/発表者名: Honjoh, S., Yamamoto, T., Uno, M. and Nishida, E.
  • 雑誌名: elegans. Nature 457 ページ: 726-730
• [雑誌論文] Regulation of the ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • 著者名/発表者名: Hanafusa, H., Matsumoto, K. and Nishida, E.
  • 雑誌名: Nature Cell Biol 11 ページ: 106-109
• [雑誌論文] Singmalling through RHEB-1 mediates intermittent fasting-induced lingevity in C. elegans (2009)
  • 著者名/発表者名: Honjoh, S., et al.
  • 雑誌名: Nature 457 ページ: 726-730
  • 査読あり
• [雑誌論文] Regulation of ERK activity duration by Sprouty contributes to dorsoventral patterning (2009)
  • 著者名/発表者名: Hanafusa, H., et al.
  • 雑誌名: Nature Cell Biol. 11 ページ: 106-109
  • 査読あり
• [雑誌論文] Ripples from neighbouring transcription (2008)
  • 著者名/発表者名: Ebisuya, M., Yamamoto, T., Nakajima, M. and Nishida, E.
  • 雑誌名: Nature Cell Biol 10 ページ: 1106-1113
• [雑誌論文] FGF induces oscillations of Hes1 expression and Ras/ERK activation (2008)
  • 著者名/発表者名: Nakayama, K., Satoh, T., Igari, A., Kageyama, R. and Nishida, E.
  • 雑誌名: Curr. Biol 18
• [雑誌論文] Myt1 protein kinase is essential for Golgi and ER assenmbly during mitotic exit (2008)
  • 著者名/発表者名: Nakajima, H., Yonemura, S., Murata, M., Nakamura, N., Piwnica-Worms, H. and Nishida, E.
  • 雑誌名: J. Cell Biol 181 ページ: 89-103
• [雑誌論文] FGF induces oscillations of Hes1 expression and Ras/ERK activation. (2008)
  • 著者名/発表者名: Nakayama, K., et. al.
  • 雑誌名: Curr. Biol. (in press)
  • 査読あり
• [雑誌論文] PtdIns(3, 4, 5)P3 regulates spindle orientation in adherent cells (2007)
  • 著者名/発表者名: Toyoshima, F., Matsumura, S., Morimoto, H., Mitsushima, M. and Nishida, E.
  • 雑誌名: Dev. Cell 13 ページ: 796-811
• [雑誌論文] Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1-and myosin X-dependent manner (2007)
  • 著者名/発表者名: Toyoshima, F., and Nishida, E.
  • 雑誌名: EMBO J 26 ページ: 1487-1498
• [雑誌論文] Wntll stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through (2007)
  • 著者名/発表者名: Yamanaka, H., and Nishida, E.
  • 雑誌名: Genes Cells 12 ページ: 961-967
  • 査読あり
• [雑誌論文] Requirement for ERK MAP kinase in mouse preimplantation development. (2007)
  • 著者名/発表者名: Maekawa, M., et. al.
  • 雑誌名: Development 134 ページ: 2751-2759
  • 査読あり
• [雑誌論文] Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis. (2007)
  • 著者名/発表者名: Kondoh, K. et al.
  • 雑誌名: J.Biol.Chem. 282 ページ: 3058-3065
• [雑誌論文] Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. (2007)
  • 著者名/発表者名: Toyoshima, F., Nishida, E.
  • 雑誌名: EMBO J. 26 ページ: 1487-1498
• [雑誌論文] Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression (2006)
  • 著者名/発表者名: Yamamoto, T., Ebisuya, M., Ashida, F., Okamoto, K., Yonehara, S. and Nishida, E.
  • 雑誌名: Curr. Biol 16 ページ: 1171-1182
• [雑誌論文] MAPK signalling : ERK5 versus ERK1/2 (2006)
  • 著者名/発表者名: Nishimoto, S. and Nishida, E.
  • 雑誌名: EMBO Rep 7 ページ: 782-786
• [雑誌論文] XGAP, an ArfGAP, is required for polarized localization of PAR proteins and cell polarity in Xenopus gastrulation. (2006)
  • 著者名/発表者名: Hyodo-Miura, J. et al.
  • 雑誌名: Dev.Cell 11 ページ: 69-79
• [雑誌論文] Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. (2006)
  • 著者名/発表者名: Yamamoto, T. et al.
  • 雑誌名: Curr.Biol. 12 ページ: 1171-1182
• [雑誌論文] MAPK signalling : ERK5 versus ERK1/2. (2006)
  • 著者名/発表者名: Nishimoto, S., Nishida, E.
  • 雑誌名: EMBO Rep. 7 ページ: 782-786
• [雑誌論文] Regulatory mechanisms and functions of MAP kinase signaling pathways. (2006)
  • 著者名/発表者名: Imajo, M. et al.
  • 雑誌名: IUBMB Life 58 ページ: 312-317
• [雑誌論文] Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and (2006)
  • 著者名/発表者名: Kondoh, K. et al.
  • 雑誌名: Mol. Cell. Biol. 26 ページ: 1679-1690
• [雑誌論文] Requirement of the MAP kinase signaling pathways for mouse preimplantation development (2005)
  • 著者名/発表者名: Maekawa, M., Yamamoto, T., Tanoue, T., Yuasa, Y., Chisaka, O. and Nishida, E.
  • 雑誌名: Development 132 ページ: 1173-1783
• [雑誌論文] Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development (2005)
  • 著者名/発表者名: Nishimoto, S., Kusakabe, M. and Nishida, E.
  • 雑誌名: EMBO Rep 6 ページ: 1064-1069
• [雑誌論文] Resetting of peripheral circadian clock by prostaglandin E2. (2005)
  • 著者名/発表者名: Tsuchiya, Y. et al.
  • 雑誌名: EMBO Rep. 6 ページ: 256-261
• [雑誌論文] Xenopus ILK (integrin-linked kinase) is required for morphogenetic movements during gastrulation. (2005)
  • 著者名/発表者名: Yasunaga, T. et al.
  • 雑誌名: Genes Cells 10 ページ: 369-379
• [雑誌論文] Requirement of the MAP kinase signaling pathways for mouse preimplantation development. (2005)
  • 著者名/発表者名: Maekawa, M. et al.
  • 雑誌名: Development 132 ページ: 1173-1783
• [雑誌論文] Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development. (2005)
  • 著者名/発表者名: Nishimoto, S. et al.
  • 雑誌名: EMBO Rep. 6 ページ: 1064-1069
• [雑誌論文] The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in (2005)
  • 著者名/発表者名: Inoue, H. et al.
  • 雑誌名: Genes Dev. 19 ページ: 2278-2283
• [雑誌論文] Requirement of the MAP kinase signaling pathways for mouse preimplantation development. (2005)
  • 著者名/発表者名: Maekawa, M. et al.
  • 雑誌名: Development (In press)
• [雑誌論文] The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC (2004)
  • 著者名/発表者名: Kusakabe, M. and Nishida, E.
  • 雑誌名: EMBO J 23 ページ: 4190-4201
• [雑誌論文] Sef is a spatial regulator for Ras/MAP kinase signaling (2004)
  • 著者名/発表者名: Torii, S., Kusakabe, M., Yamamoto, T., Maekawa, M. and Nishida, E.
  • 雑誌名: Dev. Cell 7 ページ: 33-44
• [雑誌論文] ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing (2004)
  • 著者名/発表者名: Matsubayashi, Y., Ebisuya, M., Honjoh, S. and Nishida, E.
  • 雑誌名: Curr. Biol 14 ページ: 731-735
• [雑誌論文] Sef is a spatial regulator for Ras/MAP kinase signaling. (2004)
  • 著者名/発表者名: Torii, S. et al.
  • 雑誌名: Dev.Cell 7 ページ: 33-44
• [雑誌論文] Shp2, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. (2004)
  • 著者名/発表者名: Hanafusa, H. et al.
  • 雑誌名: J.Biol.Chem. 279 ページ: 22992-22995
• [雑誌論文] The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC. (2004)
  • 著者名/発表者名: Kusakabe, M. et al.
  • 雑誌名: EMBO J. 23 ページ: 4190-4201
• [学会発表] 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)
  • 著者名/発表者名: Endo, T., Kusakabe, M., Sunadome, K., Yamamoto, T. and Nishida, E.
  • 学会等名: The 12th International Xenopus conference
  • 発表場所: Eurostrand Hotel, Leiwen, Germany
• [学会発表] Functional analysis of EIG121L (estrogen induced gene 121-like) in early Xenopus development (2008)
  • 著者名/発表者名: Araki, T., Kusakabe, M. and Nishida, E.
  • 学会等名: The 12th International Xenopus Conference
  • 発表場所: Eurostrand Hotel, Leiwen, Germany
• [学会発表] Functional analysis of EIG121L in early Xenopus development (2008)
  • 著者名/発表者名: Araki, T., et al.
  • 学会等名: The 12th International Xenopus Conference
  • 発表場所: Leiwen, Germany
• [学会発表] Rheb is required for intermittent fasting-induced lifespan extension. (2007)
  • 著者名/発表者名: Honjoh, S., and Nishida, E.
  • 学会等名: 16th International C. elegans meeting
  • 発表場所: University of California
  • 年月日: 2007-06-07
• [学会発表] Rheb is required for intermittent fasting-induced life span extension (2007)
  • 著者名/発表者名: Honjoh, S. and Nishida, E.
  • 学会等名: 16th International C
  • 発表場所: elegans meeting University of California
• [学会発表] Antagonistic Interactions between the Retinoic Acid Receptor and Ras/ERK Signaling Pathways in Colorectal Cancer Cells (2007)
  • 著者名/発表者名: Imajo, M., Kondoh, K., Yamamoto, T., Nakayama, K. and Nishida, E.
  • 学会等名: The 47th Annual Meeting of the American Society for Cell Biology
  • 発表場所: Washington Convention Center, Washington DC, USA
• [学会発表] A screen for genes comprising C. elegans MAPK cascades that affect the lifespan (2006)
  • 著者名/発表者名: Okuyama, T., Kano, K., Ookuma, S., Inoue, H., Hisamoto, N., Matsumoto, K. and Nishida, E.
  • 学会等名: The 2nd East Asia C. elegans Meeting
  • 発表場所: The Hoam Convention Center, Seoul National University, Seoul, Korea
• [学会発表] Signal transduction by the ERK family of MAP kinases (2006)
  • 著者名/発表者名: Nishida, E
  • 学会等名: International Symposium of Kobe University 21st century COE program on Signal transduction In Memory of Prof. Yasutomi Nishizuka
  • 発表場所: International Conference Center Kobe, Japan
• [学会発表] The MEK5-ERK5 pathway is essential for Xenopus neural differentiation (2005)
  • 著者名/発表者名: Nishimoto, S., Kusakabe, M. and Nishida, E.
  • 学会等名: 15th International Society of Developmental Biologists Congress 2005
  • 発表場所: Sydney, Australia
• [学会発表] Extension of the lifespan of Caenorhabditis elegans by beta-the lifespan of Caenorhabditis elegans by betacarotene (2005)
  • 著者名/発表者名: Ookuma, S., Taniguchi, E., Bamba, C., Kanoh, K., Hashimoto, Y. and Nishida, E
  • 学会等名: 15th International C. elegans Conference
  • 発表場所: University of California, Los Angeles, California, USA
• [学会発表] Signal transduction by the ERK family of MAP kinases (2004)
  • 著者名/発表者名: Nishida, E
  • 学会等名: The First Shanghai Symposium On Signal Transduction And Cancer
  • 発表場所: Shanghai, China