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Analysis of a novel signaling pathway which links G0 to M phases via centrosomal kinases

Research Project

Project/Area Number 22570185
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOsaka University

Principal Investigator

YABUTA Norikazu  大阪大学, 微生物病研究所, 准教授 (10343245)

Co-Investigator(Renkei-kenkyūsha) NOJIMA Hiroshi  大阪大学, 微生物病研究, 教授 (30156195)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords中心体 / キナーゼ / M 期 / Lats / Aurora / Hippo / リン酸化 / G0 期 / M期 / G0期 / GO期
Research Abstract

Chromosomal instability (CIN) that is one of the essential properties of tumor malignancy is associated with abnormal centrosome amplification and disturbed mitotic (M phase) checkpoint control, suggesting that certain centrosomal kinases cause induction of CIN. Furthermore, abnormal cell growth due to inability to enter the G0 phase is another important trait of cancer. In this study, we demonstrate that the centrosomal kinases, Lats1 and Lats2, control the mitotic checkpoint through centrosomal integrity and chromosomal segregation and prevent abnormal cell growth. These results suggest that Lats1/2 kinases comprise a novel signaling pathway which links G0 to M phases of the cell cycle.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (34 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (8 results) Book (8 results) Remarks (4 results)

  • [Journal Article] Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury.2013

    • Author(s)
      Del Re DP, Yang Y, Nakano N, Cho J, Zhai P, Yamamoto T, Zhang N, Yabuta N, Nojima H, Pan D, Sadoshima J
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 6 Pages: 3977-88

    • DOI

      10.1074/jbc.m112.436311

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability.2013

    • Author(s)
      Yabuta N, Mukai S, Okamoto A, Okuzaki D, Suzuki H, Torigata K, Yoshida K, Okada N, Miura D, Ito A, Ikawa M, Okabe M, Nojima H.
    • Journal Title

      Journal of Cell Science

      Volume: 126 Issue: 2 Pages: 508-520

    • DOI

      10.1242/jcs.113431

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer susceptibility and embryonic lethality in Mobla/lb double-mutant mice.2012

    • Author(s)
      Nishio M.
    • Journal Title

      J Clin Invest.

      Volume: 122 Issue: 12 Pages: 4505-4518

    • DOI

      10.1172/jci63735

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'γ subunit2012

    • Author(s)
      Naito Y, Shimizu H, Kasama T, Sato J, Tabara H, Okamoto A, Yabuta N, Nojima H
    • Journal Title

      Cell Cycle

      Volume: 11 Issue: 3 Pages: 604-16

    • DOI

      10.4161/cc.11.3.19114

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation.2012

    • Author(s)
      Zhang K, Rodriguez-Aznar E, Yabuta N,Owen RJ, Mingot JM, Nojima H, Nieto MA, Longmore GD
    • Journal Title

      EMBO J

      Volume: 31 Issue: 1 Pages: 29-43

    • DOI

      10.1038/emboj.2011.357

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B' gamma subunit2012

    • Author(s)
      Naito Y, Shimizu H, Kasama T, Sato J, Tabara H, Okamoto A, Yabuta N, Nojima H
    • Journal Title

      Cell Cycle

      Volume: VOL 11 Pages: 604-616

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction2011

    • Author(s)
      Tabara H, Naito Y, Ito A, Katsuma A, Sakurai MA, Ohno S, Shimizu H, Yabuta N, Nojima H
    • Journal Title

      PLoS One

      Volume: 6 Issue: 10 Pages: e26034-e26034

    • DOI

      10.1371/journal.pone.0026034

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis.2011

    • Author(s)
      Yabuta N, Mukai S, Okada N, Aylon Y, Nojima H
    • Journal Title

      Cell Cycle

      Volume: 10 Issue: 16 Pages: 2724-36

    • DOI

      10.4161/cc.10.16.16873

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel Chk1/2-Lats2 -14-3-3 signaling pathway regulates P-body formation in response to UV damage2011

    • Author(s)
      Okada N, Yabuta N, Suzuki H, Aylon Y, Oren M, Nojima H
    • Journal Title

      J Cell Sci

      Volume: 124 Issue: 1 Pages: 57-67

    • DOI

      10.1242/jcs.072918

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts from blood2011

    • Author(s)
      Okuzaki D, Kimura S, Yabuta N, Ohmine T, Nojima H
    • Journal Title

      BMC Clinical Pathology

      Volume: VOL 11 : 9 Pages: 1-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis2011

    • Author(s)
      Yabuta N, Mukai S, Okada N, Aylon Y, Nojima H
    • Journal Title

      Cell Cycle

      Volume: VOL 11 Pages: 2724-2736

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage.2011

    • Author(s)
      Okada N, Yabuta N, Suzuki H, Aylon Y, Oren M, Nojima H.
    • Journal Title

      Journal of Cell Science

      Volume: VOL124 Pages: 57-67

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP12010

    • Author(s)
      Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, Oren M
    • Journal Title

      Genes Dev

      Volume: 24 Issue: 21 Pages: 2420-9

    • DOI

      10.1101/gad.1954410

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1.2010

    • Author(s)
      Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, Oren M.
    • Journal Title

      Genes & Development

      Volume: VOL24 Pages: 2420-2429

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Lats1 and Lats2 kinases regulate chromosomal instability2011

    • Author(s)
      藪田紀一、向井智美、鈴木宏和、岡田宣宏、三浦大作、奥崎大介、野島博
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Lats1 and Lats2 kinases regulate chromosomal instability2011

    • Author(s)
      藪田紀一
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都府)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] The Aurora-A-Lats1/2-Aurora-B axis is a novel pathway that regulates precise mitotic progression2010

    • Author(s)
      藪田紀一、向井智美、岡田宣宏、鈴木宏和、野 島 博
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2012 Final Research Report
  • [Presentation] The Aurora-A-Lats1/2-Aurora-B axis is a novel pathway that regulates precise mitotic progression.2010

    • Author(s)
      薮田紀一
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] An Aurora-A-Lats2 -Aurora-B pathway is required for accurate mitotic progression2010

    • Author(s)
      Yabuta N, Nojima H
    • Organizer
      The Second Workshop on the HIPPO Tumor Suppressor
    • Place of Presentation
      Pathway (Rome, Italy)
    • Year and Date
      2010-12-04
    • Related Report
      2012 Final Research Report
  • [Presentation] An Aurora-A-Lats2-Aurora-B pathway is required for accurate mitotic progression.2010

    • Author(s)
      薮田紀一
    • Organizer
      The Second Workshop on the HIPPO Tumor Suppressor Pathway
    • Place of Presentation
      Palazzo Chigi, Ariccia, Rome (Italy)
    • Year and Date
      2010-11-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] The tumor suppressor Lats2 is a signaling nexus of Aurora-A to Aurora-B during mitosis2010

    • Author(s)
      藪田紀一、岡田宣宏、向井智美、鈴木宏和、野島博
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
    • Related Report
      2012 Final Research Report
  • [Presentation] The tumor suppressor Lats2 is a signaling nexus of Aurora-A to Aurora-B during mitosis.2010

    • Author(s)
      薮田紀一
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Book] 「細胞周期同調法 他2稿」DVD で見るバイオ実験2013

    • Author(s)
      藪田紀一
    • Total Pages
      12
    • Publisher
      講談社
    • Related Report
      2012 Final Research Report
  • [Book] "Hippo in Cell Cycle and Mitosis" The Hippo Signaling Pathway and Cancer2013

    • Author(s)
      Yabuta N, Nojima H
    • Total Pages
      23
    • Publisher
      Springer
    • Related Report
      2012 Final Research Report
  • [Book] DVDで見るバイオ実験 (編 野島博)、「細胞周期同調法」の項、他2稿2013

    • Author(s)
      藪田紀一
    • Total Pages
      12
    • Publisher
      講談社
    • Related Report
      2012 Annual Research Report
  • [Book] The Hippo Signaling Pathway and Cancer (Eds. Moshe Oren, Yael Aylon), Chapter 10 “Hippo in Cell Cycle and Mitosis”2013

    • Author(s)
      Yabuta N, Nojima H
    • Total Pages
      23
    • Publisher
      Springer
    • Related Report
      2012 Annual Research Report
  • [Book] 「DNA 損傷シグナリング」シグナル伝達キーワード事典2012

    • Author(s)
      藪田紀一、野島博
    • Total Pages
      3
    • Publisher
      羊土社
    • Related Report
      2012 Final Research Report
  • [Book] シグナル伝達キーワード事典 (編 山本雅・仙波憲太郎・山梨裕司)、「DNA損傷シグナリング」の項2012

    • Author(s)
      藪田紀一、野島博
    • Total Pages
      3
    • Publisher
      羊土社
    • Related Report
      2012 Annual Research Report
  • [Book] 「細胞増殖・細胞死制御と Hippo pathway: Lats キナーゼを中心に」細胞工学2011

    • Author(s)
      藪田紀一、野島博
    • Total Pages
      7
    • Publisher
      秀潤社
    • Related Report
      2012 Final Research Report
  • [Book] 細胞工学30巻9号特集「Hippo Pathway-癌・細胞死・再生の新たな鍵を握る器官サイズ制御シグナル」「細胞増殖・細胞死制御とHippo pathway : Latsキナーゼを中心に」の項2011

    • Author(s)
      藪田紀一、野島博
    • Total Pages
      7
    • Publisher
      秀潤社
    • Related Report
      2011 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://molgenet.biken.osaka-u.ac.jp/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 大阪大学微生物病研究所分子遺伝研究分野ホームページ

    • URL

      http://molgenet.biken.osaka-u.ac.jp/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/lab/molgenet/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/lab/molgenet/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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