Signal transduction networks regulating life span and development

• Project/Area Number: 21227004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Kyoto University
• Principal Investigator: NISHIDA Eisuke 京都大学, 生命科学研究科, 教授 (60143369)
• Project Period (FY): 2009-05-11 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥213,200,000 (Direct Cost: ¥164,000,000、Indirect Cost: ¥49,200,000); Fiscal Year 2013: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2012: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2011: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2010: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2009: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000)
• Keywords: 寿命 / 発生 / シグナル伝達 / 寿命制御 / 老化 / 食餌制限 / 飢餓ストレス応答 / 初期胚発生 / ストレス耐性 / AP-1 / MAPキナーゼ経路 / Hippo経路 / カロリー制限 / 断続的飢餓 / ERK MAPキナーゼ / SGK-1

Research Abstract

We found that a signaling pathway consisting of the stress-responsive MAP kinase JNK and the transcription factor AP-1 is essential for fasting-induced extension of life span in C. elegans. We also found that the kinase SGK1 promotes ectodermal cell survival during early Xenopus embryonic development through a non-cell-autonomous signaling pathway. Furthermore, we identified a signaling pathway regulating cell fusion during mammalian skeletal muscle differentiation. Also, we identified an antagonistic interaction between skeletal muscle and adipose differentiation programs.

Assessment Rating

Verification Result (Rating)

A+

Research Products

• [Journal Article] Antagonism between the master regulators of differentiation ensures the discreteness and robustness of cell fates (2014)
  • Author(s): Sunadome, K., Suzuki, T., Usui, M., Ashida, Y. and Nishida, E
  • Journal Title: Mol. Cell Volume: 54 Issue: 3 Pages: 526-535
  • DOI: 10.1016/j.molcel.2014.03.005
  • Peer Reviewed
• [Journal Article] Foxd1 is a mediator and indicator of the cell reprogramming process (2014)
  • Author(s): Makito Koga, Mitsuhiro Matsuda, Teruhisa Kawamura, Takahiro Sogo, Asako Shigeno, Eisuke Nishida, Miki Ebisuya
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 3197-3197
  • DOI: 10.1038/ncomms4197
  • Peer Reviewed
• [Journal Article] A fasting-responsive signaling pathway that extends life span in C. elegans (2013)
  • Author(s): Uno, M., Honjoh, S., Matsuda, M., Hoshikawa, H., Kishimoto, S., Yamamoto, T., Ebisuya, M., Yamamoto, T., Matsumoto, K. and Nishida, E
  • Journal Title: Cell Rep Volume: 3 Issue: 1 Pages: 79-91
  • DOI: 10.1016/j.celrep.2012.12.018
  • Peer Reviewed
• [Journal Article] The casein kinase 2-nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression (2013)
  • Author(s): Tsuchiya Y. et al.
  • Journal Title: Mol Cell Biol. Volume: 33 Issue: 17 Pages: 3461-3472
  • DOI: 10.1128/mcb.01271-12
  • Peer Reviewed
• [Journal Article] Global Splicing Pattern Reversion during Somatic Cell Reprogramming (2013)
  • Author(s): Ohta, S., Nishida, E., Yamanaka, S., and Yamamoto, T.
  • Journal Title: Cell Reports Volume: 5 Issue: 2 Pages: 357-366
  • DOI: 10.1016/j.celrep.2013.09.016
  • Peer Reviewed
• [Journal Article] The protein kinase MLTK regulateschondrogenesis by inducing the transcriptionfactor Sox6 (2012)
  • Author(s): Suzuki, T., Kusakabe, M., Nakayama, K. and Nishida, E
  • Journal Title: Development Volume: 139 Issue: 16 Pages: 2988-2998
  • DOI: 10.1242/dev.078675
  • Peer Reviewed
• [Journal Article] A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling (2012)
  • Author(s): Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E
  • Journal Title: The EMBO Journal Volume: 31 Issue: 5 Pages: 1109-1122
  • DOI: 10.1038/emboj.2011.487
  • Peer Reviewed
• [Journal Article] Synthetic signal propagation through direct cell-cell interaction. (2012)
  • Author(s): Matsuda M. et al.
  • Journal Title: Sci. Signal. Volume: 5 Issue: 220
  • DOI: 10.1126/scisignal.2002764
  • Peer Reviewed
• [Journal Article] Identification and characterization of Xenopus kctd15, an ectodermal gene repressed by the FGF pathwav (2012)
  • Author(s): Takahashi C., et al
  • Journal Title: Int.J.Dev.Biol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] A molecular mechanism that links Hippo signalling to the inhibition of Wnt/beta-catenin signalling (2012)
  • Author(s): Imajo M., et al
  • Journal Title: EMBO J. Volume: 31 Pages: 1109-11222
  • Peer Reviewed
• [Journal Article] Two sides of lifespan regulating genes : pro-longevity or anti-longevity? (2011)
  • Author(s): Honjoh, S. and Nishida, E
  • Journal Title: J. Biochem Volume: 149 Issue: 4 Pages: 381-388
  • DOI: 10.1093/jb/mvr026
  • Peer Reviewed
• [Journal Article] ERK5 regulates muscle cell fusion through Klf transcription factors (2011)
  • Author(s): Sunadome, K., Yamamoto, T., Ebisuya, M., Kondoh, K., Sehara-Fujisawa, A. and Nishida, E
  • Journal Title: Dev. Cell Volume: 20 Issue: 2 Pages: 192-205
  • DOI: 10.1016/j.devcel.2010.12.005
  • Peer Reviewed
• [Journal Article] The kinase SGK1 in the endoderm and mesoderm promotes ectodermal survival by down-regulating components of the death-inducing signaling complex (2011)
  • Author(s): Endo, T., Kusakabe, M., Sunadome, K., Yamamoto, T. and Nishida, E
  • Journal Title: Sci. Signal Volume: 4 Issue: 156
  • DOI: 10.1126/scisignal.2001211
  • Peer Reviewed
• [Journal Article] A transmembrane protein EIG121L is required for epidermal differentiation during early embryonic development (2011)
  • Author(s): Araki, T., Kusakabe, M. and Nishida, E
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 8 Pages: 6760-6768
  • DOI: 10.1074/jbc.m110.177907
  • Peer Reviewed
• [Journal Article] ERK5 regulates muscle cell fusion through Klf transcription factors (2011)
  • Author(s): Sunadome K., et al
  • Journal Title: Dev.Cell Volume: 20 Pages: 192-205
  • Peer Reviewed
• [Journal Article] The kinase SGK1 in the endoderm and mesoderm promotes ectodermal survival by down-regulating components of the death-inducing signaling complex (2011)
  • Author(s): Endo T., et al.
  • Journal Title: Sci.Signal. Volume: 4
  • Peer Reviewed
• [Journal Article] A transmembrane protein EIG121L is required for epidermal differentiation during early embryonic development (2011)
  • Author(s): Araki T., et al.
  • Journal Title: J.Biol.Chem. Volume: 286 Pages: 6760-6768
  • Peer Reviewed
• [Journal Article] Human Tribbles homolog 1 functions as a negative regulator of retinoic acid receptor (2010)
  • Author(s): Imajo, M. and Nishida, E
  • Journal Title: Genes Cells Volume: 15 Issue: 10 Pages: 1089-1097
  • DOI: 10.1111/j.1365-2443.2010.01445.x
  • Peer Reviewed
• [Journal Article] Revolving movement of a dynamic cluster of actin filaments during mitosis (2010)
  • Author(s): Mitsushima, M., Aoki, K., Ebisuya, M., Matsumura, S., Yamamoto, T., Matsuda, M., Toyoshima, F. and Nishida, E.
  • Journal Title: J. Cell Biol Volume: 191 Issue: 3 Pages: 453-462
  • DOI: 10.1083/jcb.201007136
  • Peer Reviewed
• [Journal Article] The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans (2010)
  • Author(s): Okuyama, T., Inoue, H., Ookuma, S., Satoh, T., Kano, K., Honjoh, S., Hisamoto, N., Matsumoto, K. and Nishida, E.
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 39 Pages: 30274-30281
  • DOI: 10.1074/jbc.m110.146274
  • Peer Reviewed
• [Journal Article] The DM domain transcription factor MAB-3 regulates male hypersensitivity to oxidative stress in Caenorhabditis elegans (2010)
  • Author(s): Inoue, H. and Nishida, E.
  • Journal Title: Cell Biol Volume: 14 Issue: 14 Pages: 3453-3459
  • DOI: 10.1128/mcb.01459-09
  • Peer Reviewed
• [Journal Article] CrkL is a novel target of Sprouty2 in fibroblast growth factor signaling (2010)
  • Author(s): Satoh, T., Torii, S., Nakayama, K. and Nishida, E.
  • Journal Title: Genes Cells Volume: 15 Issue: 3 Pages: 161-168
  • DOI: 10.1111/j.1365-2443.2009.01373.x
  • Peer Reviewed
• [Journal Article] The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans (2010)
  • Author(s): Okuyama T., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 30274-30281
  • 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. and Nishida, E.
  • Journal Title: Sci. Signal Volume: 2 Issue: 73 Pages: 717-726
  • DOI: 10.1126/scisignal.2000305
  • Peer Reviewed
• [Journal Article] Involvement of the protein kinase CK2 in the regulation of mammalian circadian rhythms (2009)
  • Author(s): Tsuchiya Y., et al.
  • Journal Title: Sci.Signal. 2
  • Peer Reviewed
• [Journal Article] Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans (2009)
  • Author(s): Hashimoto Y., et al.
  • Journal Title: Genes Cells 14 Pages: 717-726
  • Peer Reviewed
• [Presentation] 細胞内シグナル伝達：寿命制御と組織ホメオスタシス維持機構 (2014)
  • Author(s): 西田栄介
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] MAP2からＭＡＰキナーゼ、そしてシグナル伝達ネットワーク研究へ (2014)
  • Author(s): 西田栄介
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸 国際会議場
  • Invited
• [Presentation] MAP2からMAPキナーゼ, そしてシグナル伝達ネットワーク研究へ (2013)
  • Author(s): 西田栄介
  • Organizer: 第36回日本分子生物学会年会シンポジウム「シグナル伝達温故知新～発見者に聴く～」
  • Place of Presentation: 神戸ポートアイランド, 神戸市, 日本
• [Presentation] 細胞内シグナル伝達 : 寿命制御と組織ホメオスタシス維持機構 (2013)
  • Author(s): 西田栄介
  • Organizer: 第86回日本生化学会大会特別講演
  • Place of Presentation: パシフィコ横浜, 横浜市, 日本
• [Presentation] Molecular mechanisms underlying fasting-induced longevity in C. elegans. (2013)
  • Author(s): Kishimoto, S., Uno, M., Kaneko, Y., Nishioka, S. and Nishida, E.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics
  • Place of Presentation: Coex, Seoul, Korea
• [Presentation] Identification of signaling molecules that regulate renal branching morphogenesis. (2012)
  • Author(s): Takayama, M., Hiramatsu, T. and Nishida, E.
  • Organizer: Joint meeting of the BSDB/BSCB/JSDB
  • Place of Presentation: University of Warwick, Coventry, UK
• [Presentation] Identification and characterization of Xenopus kctd15, an FGF-repressed ectodermal gene. (2012)
  • Author(s): Takahashi, C., Suzuki, T., Nishida, E. and Kusakabe, M
  • Organizer: Joint meeting of the BSDB/BSCB/JSDB
  • Place of Presentation: The University of Warwick, Coventry, UK
• [Presentation] 飢餓による寿命延長の分子機構 (2012)
  • Author(s): 宇野雅晴、西田栄介
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場 マリンメッセ福岡
  • Invited
• [Presentation] 腸上皮ホメオスタシスを制御するシグナル伝達経路の解析 (2011)
  • Author(s): 今城正道、西田栄介
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] A conserved JNK/AP-1 module is a key mediator of intermittent fasting-induced longevity in C. elegans. (2011)
  • Author(s): Uno, M., Honjoh, S. and Nishida, E.
  • Organizer: 18th international C. elegans meeting
  • Place of Presentation: University of California, Los Angeles, California, USA
• [Presentation] Role of Sox5 and Sox6 in Xenopus development (2010)
  • Author(s): Suzuki T., et al.
  • Organizer: 13^<th> International Xenopus Conference
  • Place of Presentation: Alberta, Canada
  • Year and Date: 2010-09-14
• [Presentation] Role of Sox5 and Sox6 in Xenopus development (2010)
  • Author(s): Suzuki, T., Kusakabe, M. and Nishida, E.
  • Organizer: 13th International Xenopus Conference
  • Place of Presentation: Fairmont Chateau Lake Louise, Lake Louise, Alberta, Canada
• [Presentation] A novel Regulator of the BMP Pathway required for epidermal differentiation during early embryonic development. (2010)
  • Author(s): Araki, T., Kusakabe, M. and Nishida, E.
  • Organizer: 13th International Xenopus Conference
  • Place of Presentation: Fairmont Chateau Lake Louise, Lake Louise, Alberta, Canada
• [Presentation] The age-dependent changes in the gene expression profile in C. elegans. (2010)
  • Author(s): Honjoh, S., Yamamoto, T. and Nishida, E.
  • Organizer: EMBO Conference Series, C. elegans Development and Gene Expression, EMBL Advanced Training Centre
  • Place of Presentation: Heidelberg, Germany
• [Presentation] Requirement for the stress-responsive MAP kinase KGB-1 signalling pathway in intermittent fasting-induced longevity in C. elegans. (2009)
  • Author(s): Uno, M., Honjoh, S. and Nishida, E.
  • Organizer: 17th International C. elegans Meeting
  • Place of Presentation: UCLA, Los Angeles, Calfornia, USA
• [Presentation] 線虫C.elegansにおける食餌制限による寿命延長の分子機構 (2009)
  • Author(s): 本城咲季子, ら
  • Organizer: 日本基礎老化学会第32回大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 初期胚発生における新規の二重キナーゼ機構 (2009)
  • Author(s): 日下部杜央、西田栄介
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://www.lif.kyoto-u.ac.jp/labs/signal/