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2013 Fiscal Year Final Research Report

Characterization of the centrosomal kinases that regulate chromosome instability in cancer cells.

Research Project

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Project/Area Number 23370086
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

NOJIMA HIROSHI  大阪大学, 微生物病研究所, 教授 (30156195)

Co-Investigator(Renkei-kenkyūsha) YABUTA Norikazu  大阪大学, 微生物病研究所, 准教授 (10343245)
OKUZAKI Daisuke  大阪大学, 微生物病研究所, 助教 (00346131)
NAITO Yoko  大阪大学, 微生物病研究所, 特任研究員 (10553026)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords染色体不安定性 / 中心体 / キナーゼ / M期チェックポイント / Lats / GAK
Research Abstract

Tumor malignancy promotes cell invasion and metastasis, which is one of the factors that hamper effective cancer therapy. Tumor malignancy means that cancer cells frequently cause missegregation of chromosomes on every cell division to generate two daughter cells with distinct chromosome quantity; this cancer specific feature is called "chromosomal instability". In this study, we show that the centrosomal kinases, Lats1/2 and GAK, form three novel signaling pathways and regulate the stability of chromosomes: they are Aurora-A-Lats1/2-Aurora-B (ALB) and Chk1-Lats2-14-3-3-P-body (CLP) pathways for Lats1/2 and GAK-PP2A-B'gamma-Chk2/Condensin II (GBC) pathway for GAK. To realize efficient analysis, we generated knockout mice lacking Lats1, Lats2, GAK, Cyclin G1 and/or Cyclin G2 genes, and Lats2-defective cancer cells using TALEN/Crispr_Cas systems.

  • Research Products

    (42 results)

All 2014 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (17 results) Book (5 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A functional interaction between Hippo-Y AP signalling and FoxO1 mediates the oxidative stress response2014

    • Author(s)
      Shao D, Zhai P, Del Re DP, Sciarretta S, Y abuta N, Nojima H, Lim DS, Pan D, Sadoshima J
    • Journal Title

      Nat. Commun

      Volume: 5 Pages: 3315

    • DOI

      10.1038/ncomms4315

    • Peer Reviewed
  • [Journal Article] Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats : gene expression profiles in the brain2014

    • Author(s)
      Yoshida M, Watanabe Y, Yamanishi K, Yamashita A, Yamamoto H, Okuzaki D, Shimada K, Nojima H, Yasunaga T, Okamura H, Matsunaga H, Yamanishi H
    • Journal Title

      Int. J. Mol. Med

      Volume: 33 Pages: 887-896

    • DOI

      10.3892/ijmm.2014.1631

    • Peer Reviewed
  • [Journal Article] CAWS administration increases the expression of interferon γ and complement factors that lead to severe vasculitis in DBA/2 mice2013

    • Author(s)
      Nagi-Miura N, Okuzaki D, T origata K, Sakurai MA, Ito A, Ohno N, Nojima H
    • Journal Title

      BMC Immun

      Volume: 14 Pages: 44

    • DOI

      10.1186/1471-2172-14-44

    • Peer Reviewed
  • [Journal Article] Ficolin-1 is up-regulated in leukocytes and glomeruli from microscopic polyangiitis patients2013

    • Author(s)
      Muso E, Okuzaki D, Kobayashi S, Iwasaki Y, Sakurai MA, Ito A, Nojima H
    • Journal Title

      Autoimmunity

      Volume: 46 Pages: 513-524

    • DOI

      10.3109/08916934.2013.822073

    • Peer Reviewed
  • [Journal Article] Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis2013

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

      J. Cell Sci

      Volume: 126 Pages: 4358-4368

    • DOI

      10.1242/jcs.125815

    • Peer Reviewed
  • [Journal Article] Recruitment of cyclin G2 to promyelocytic leukemia nuclear bodies promotes dephosphorylation of γH2AX following treatment with ionizing radiation2013

    • Author(s)
      Naito Y, Y abuta N, Sato J, Ohno S, Sakata M, Kasama T, Ikawa M, Nojima H
    • Journal Title

      Cell Cycle

      Volume: 12 Pages: 1773-1784

    • DOI

      10.4161/cc.24878

    • Peer Reviewed
  • [Journal Article] Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats2013

    • Author(s)
      Yamamoto H, Okuzaki D, Yamanishi K, Xu Y, Watanabe Y, Yoshida M, Y amashita A, Goto N, Nishiguchi S, Shimada K, Nojima H, Yasunaga T, Okamura H, Matsunaga H, Yamanishi H
    • Journal Title

      Int. J. Mol. Med

      Volume: 31 Pages: 1057-1065

    • DOI

      10.3892/ijmm.2013.1304

    • Peer Reviewed
  • [Journal Article] Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury2013

    • Author(s)
      Del Re DP, Y ang 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 Pages: 3977-88

    • DOI

      10.1074/jbc.M112.436311

    • Peer Reviewed
  • [Journal Article] N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability2013

    • 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

      J Cell Sci

      Volume: 126 Pages: 508-20

    • DOI

      10.1242/jcs.113431

    • Peer Reviewed
  • [Journal Article] Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice2012

    • Author(s)
      Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F, Chiba S, Mizuno K, Suzuki SO, Dong Y, Tokuda M, Morikawa T, Hikasa H, Eggenschwiler J, Yabuta N, Nojima H, Nakagawa K, Hata Y, Nishina H, Mimori K, Mori M, Sasaki T, Mak TW, Nakano T, Itami S, Suzuki A
    • Journal Title

      J Clin Invest

      Volume: 122 Pages: 4505-18

    • DOI

      10.1172/JCI63735

    • Peer Reviewed
  • [Journal Article] Ficolin 1 expression is elevated in the peripheral blood mononuclear cells of Takayasu's vasculitis patients2012

    • Author(s)
      Okuzaki D, Kobayashi S, Sakurai MA, T origata K, Okamoto A, Matsumoto T, Daida H, Ito A, Nojima H
    • Journal Title

      J. Mol. Biomark Diagn

      Volume: 3 Pages: 125

    • Peer Reviewed
  • [Journal Article] A simple and efficient method for the preparation of live leukocytes from peripheral blood using the LeukoCatch TM system. Adv . Biosci2012

    • Author(s)
      Okamoto A, T origata K, Sakurai MA, Okuzaki D, Fujii H, Ohmine T, Miura D, Kimura S, Yabuta N, Nojima H
    • Journal Title

      Biotech

      Volume: 3 Pages: 630-642

    • 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 Pages: 604-16

    • DOI

      10.4161/cc.11.3.19114

    • Peer Reviewed
  • [Journal Article] Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation2012

    • 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 Pages: 29-43

    • DOI

      10.1038/emboj.2011.357

    • 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 Pages: e26034

    • DOI

      10.1371/journal.pone.0026034

    • Peer Reviewed
  • [Journal Article] Microarray analysis of tonsils of IgA nephropathy patients2011

    • Author(s)
      Iwatani H, Iio K, Nagasawa Y, Yamamoto R, Horii A, Okuzaki D, Inohara H, Nojima H, Imai E, Rakugi H, Isaka Y
    • Journal Title

      Adv . Otorhinolaryngol

      Volume: 72 Pages: 75-78

    • DOI

      10.1159/000324611

    • 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: 11 Pages: 9

    • DOI

      10.1186/1472-6890-11-9

    • 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: 10 Pages: 2724-2736

    • DOI

      10.4161/cc.10.16.16873

    • Peer Reviewed
  • [Presentation] 癌抑制遺伝子 Lats1 は中心体の複製と細胞周期の進行に重要である2013

    • Author(s)
      向井智美, 吉田佳織, 岡本歩, 清成寛, 藪田紀一, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-05
  • [Presentation] CyclinG-PP2A B'γ 複合体の結合阻害を標的としたペプチド抗癌医薬の開発2013

    • Author(s)
      大野将一, 内藤陽子, 藪田紀一, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-04
  • [Presentation] M 期進行における癌抑制キナーゼLats1/2 による新たな Aurora-B の活性制御機構2013

    • Author(s)
      吉田佳織, 藪田紀一, 向井智美, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-04
  • [Presentation] がん抑制因子 Lats1/2キナーゼはがん幹細胞のスフェア形成過程を制御する2013

    • Author(s)
      福澤萌, 野崎正美, 向井智美, 岡本歩, 藪田紀一, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-04
  • [Presentation] LATS2 はエピゲノム調節機構を介して HOX cluster や DLK1 - MEG3 locusの発現を制御する2013

    • Author(s)
      鳥形康輔, 奥崎大介, 藪田紀一, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-04
  • [Presentation] Withaferin A は癌細胞選択的にオートファジーと細胞死を誘導する2013

    • Author(s)
      西川幸宏, 尾崎友紀, 篠倉悠久, 奥崎大介, 藪田紀一, 野島博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03
  • [Presentation] Lats2 phosphorylates p21 and induces apoptosis in response to UV irradiation2013

    • Author(s)
      Hirokazu Suzuki, Norikazu Yabuta, Kosuke Torigata, Nobuhiro Okada, Yael Aylon, Mosh Oren and Hiroshi Nojima
    • Organizer
      Molecular Life Sciences 2013
    • Place of Presentation
      Frankfurt, Germany
    • Year and Date
      2013-10-04
  • [Presentation] Lats2 phosphorylates p21 and induces apoptosis in response to UV irradiation2013

    • Author(s)
      Hirokazu Suzuki, Norikazu Yabuta, Kosuke Torigata, Nobuhiro Okada, Yael Aylon, Mosh Oren and Hiroshi Nojima
    • Organizer
      The 5th EMBO meeting 2013
    • Place of Presentation
      Amsterdam, Netherland
    • Year and Date
      2013-09-22
  • [Presentation] Lats2 は p21 へのリン酸化を介してアポトーシスを誘導する2013

    • Author(s)
      鈴木宏和,藪田紀一,鳥形浩輔,岡田宣宏, アイロン ヤエール, オーレン モッシュ,野島博
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-13
  • [Presentation] LATS2 依存的な新規エピジェネティック制御機構の探索2013

    • Author(s)
      鳥形康輔, 向井智美,鈴木宏和,奥崎大介, 藪田紀一, 野島博
    • Organizer
      第7回日本エピジェネティクス研究会
    • Place of Presentation
      奈良
    • Year and Date
      2013-05-30
  • [Presentation] rChum, A Novel RNA Molecule to Aid PCR Amplification and Detection of Ultralow Amount of Nucleic Acids2012

    • Author(s)
      鳥形康輔, 奥崎大介, 岡本歩, 野島博
    • Organizer
      アジア太平洋血管炎・ANCA 国際会議 (AP-VAS2012)
    • Place of Presentation
      東京
    • Year and Date
      2012-03-29
  • [Presentation] LeukoCatch, a novel tool for the preparation of leukocytes and their extracts from peripheral blood2012

    • Author(s)
      岡本歩, 奥崎大介, 鳥形康輔, 野島博
    • Organizer
      アジア太平洋血管炎・ANCA 国際会議 (AP-VAS2012)
    • Place of Presentation
      東京
    • Year and Date
      2012-03-29
  • [Presentation] Lats2 phosphorylates p21 and induces apoptosis in response to UV2011

    • Author(s)
      鈴木宏和, 岡田宣宏, 藪田紀一, 野島博
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-16
  • [Presentation] Lats2, a Hippo pathway player , also regulates the DNA damage response2011

    • Author(s)
      野島博
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-15
  • [Presentation] Lats1 キナーゼの N 末端領域は染色体安定性,腫瘍抑制に必要である2011

    • Author(s)
      向井智美, 藪田紀一, 岡本歩, 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
      2011-09-22
  • [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
  • [Presentation] N 末端領域を欠損した Lats1 キナーゼは染色体不安定性と腫瘍形成を誘導する2011

    • Author(s)
      向井智美, 藪田紀一, 岡本歩, 鈴木宏和, 岡田宣宏, 三浦大作, 奥崎大介, 野島博
    • Organizer
      第58回日本生化学会近畿支部例会
    • Place of Presentation
      大阪
    • Year and Date
      2011-05-21
  • [Book] DVD で見るバイオ実験(野島博 編)2013

    • Author(s)
      野島博
    • Total Pages
      198
    • Publisher
      講談社
  • [Book] 現代化学3月号「がん細胞のみを特異的に殺す生薬成分は有望か?」2013

    • Author(s)
      尾崎友紀, 野島博
    • Total Pages
      6
    • Publisher
      東京化学同人
  • [Book] "Hippo in Cell Cycle and Mitosis"「 The Hippo Signaling Pathway and Cancer 」2013

    • Author(s)
      Yabuta N, Nojima H
    • Total Pages
      23(199-221)
    • Publisher
      Springer
  • [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(55-57)
    • Publisher
      羊土社
  • [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(923-929)
    • Publisher
      秀潤社
  • [Remarks]

    • URL

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

  • [Patent(Industrial Property Rights)] 細胞死促進剤2014

    • Inventor(s)
      野島博
    • Industrial Property Rights Holder
      大阪大学知的財産本部
    • Industrial Property Rights Type
      管理番号K20130266
    • Industrial Property Number
      特願2014-052612
    • Filing Date
      2014-03-14

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Published: 2015-06-25  

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