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Regulation of KIF3 motor by dephosphorylation

Research Project

Project/Area Number 22590298
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionMiyagi Cancer Center Research Institute

Principal Investigator

SHIMA Hiroshi  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (10196462)

Co-Investigator(Kenkyū-buntansha) YAMASITA Youzi  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (30420045)
WATANABE Tosio  奈良女子大学, 自然科学系, 教授 (60201208)
SUGAMURA Kazuo  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 特任部長 (20117360)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords分子腫瘍学 / キネシンモーター / KIF3 / ホスファターゼ / 2重基質ホスファターゼ / 2重基質ホスファターゼ / 2重基質ボスファターゼ / 癌
Research Abstract

We identified the protein-phosphatase DUSP26 as a novel regulator of the KIF3 motor. Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Enzyme activity of the Dusp26 was shown to promote distribution of beta-catenin/N-cadherinto cell-cell junction sites, resulting in increased cell-cell adhesiveness. We also showed that DUSP26 mRNA expression was downregulated in human glioblastoma samples, and a CpG island upstream of the DUSP26 transcrptional start site was heavily methylated in glioma cell lines. These results suggest previously unidentified functions of DUSP26 in intracellular transport and cell-cell adhesion.Downregulation of DUSP26 may contribute to malignant phenotypes of glioma. We showed that DUSP13B inactivated MAPK activation in the order of selectivity, JNK=p38> ERK in cells. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1 dependent gene expression. DUSP13B is the first identified testis specific phosphatase that inhibits stress-activated MAPKs.

Report

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

    (49 results)

All 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 7 results) Presentation (31 results) Book (1 results) Remarks (1 results)

  • [Journal Article] IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas.2012

    • Author(s)
      Shibahara I, Sonoda Y, Kanamori M, Saito R, Yamashita Y, Kumabe T, Watanabe M, Suzuki H, Kato S, Ishioka C, Tominaga T.
    • Journal Title

      Int J Clin Oncol

      Volume: 17(6) Pages: 551-61

    • NAID

      10031155913

    • Related Report
      2012 Final Research Report
  • [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression,and up-regulation of its gene expression in colon carcinomas2012

    • Author(s)
      Nomura M, Shiiba K-I, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, KatakuraR, Yamashita Y, Sato M, Tanuma N, Shima H
    • Journal Title

      Oncol Rep.

      Volume: 28(3) Pages: 931-6

    • Related Report
      2012 Final Research Report
  • [Journal Article] The clathrin assembly protein PICALMis required for erythroid maturationand transferrin internalization in mice2012

    • Author(s)
      Suzuki M, Tanaka H, Tanimura A, Tanabe K, Oe N, Rai S, Kon S, Fukumoto M,Takei K, Abe T, Matsumura I, Kanakura Y, Watanabe T.
    • Journal Title

      PLoS One.

      Volume: 7(2)

    • Related Report
      2012 Final Research Report
  • [Journal Article] Sialidase NEU4 Hydrolyzes PolysialicAcids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons J.Biol.Chem.2012

    • Author(s)
      Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, Kitajima K, Higashi H, Nitta K, Shima H, and Miyagi T
    • Journal Title

      J.Biol.Chem.

      Volume: 287(18) Pages: 14816-26

    • Related Report
      2012 Final Research Report
  • [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression, and up-regulation of its gene expression in colon carcinomas2012

    • Author(s)
      Miyuki Nomura
    • Journal Title

      Oncol Rep.

      Volume: 28 Pages: 931-936

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons2012

    • Author(s)
      Kohta Takahashi
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Pages: 14816-14826

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脱リン酸化側からの、がん(脳腫瘍)診断•治療へのアプローチ2012

    • Author(s)
      島 礼
    • Journal Title

      臨床病理

      Volume: 60 Pages: 1145-1147

    • NAID

      10031147847

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons2012

    • Author(s)
      Kohta Takahashi
    • Journal Title

      Journal of Biological Chemistry

      Volume: (印刷中)(未定)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DUSP13B/TMDPinhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression2011

    • Author(s)
      Katagiri C, Masuda K, Nomura M, Tanoue K, Fujita S, Yamashita Y, Katakura R, Shiiba K, Nomura E, Sato M, Tanuma N, Shima H
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 352(1-2) Pages: 155-162

    • Related Report
      2012 Final Research Report
  • [Journal Article] DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression2011

    • Author(s)
      Chiaki Katagiri
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 351 Pages: 155-162

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression.2011

    • Author(s)
      Chiaki Katagiri
    • Journal Title

      Molecular and Cellular Biochemistry

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm2010

    • Author(s)
      Masuda K, Katagiri C, Nomura M, SatoM, Kakumoto K, Akagi T, KikuchiK, Tanuma N, Shima H
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 393 Pages: 201-206

    • Related Report
      2012 Final Research Report
  • [Journal Article] CDC25A mRNA levels significantly c orrelate with Ki-67 expression in human glioma samples2010

    • Author(s)
      Yamashita Y, Kasugai I, Sato M, Tanuma N, Sato I, Nomura M, Yamashita K,Sonoda Y, Kumabe T, Tominaga T, Katakura R, Shima H
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 100(1) Pages: 43-49

    • Related Report
      2012 Final Research Report
  • [Journal Article] The phosphatase interactor NIPP1 regulates the occupancy of the histone methyltransferase EZH2 at Polycomb targets.2010

    • Author(s)
      Van Dessel N, Beke L, Gornemann J, Minnebo N, Beullens M, Tanuma N, Shima H, Van Eynde A, Bollen M.
    • Journal Title

      Nucleic Acids Res.

      Volume: 38(21) Pages: 7500-7512

    • Related Report
      2012 Final Research Report
  • [Journal Article] MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm.2010

    • Author(s)
      Kouhei Masuda
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 393 Pages: 201-206

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CDC25A mRNA levels significantly correlate with Ki-67 expression in human glioma samples.2010

    • Author(s)
      Yoji Yamashita
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 100 Pages: 43-49

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Embryonic Lethality Caused in Mice LPP6c gene2013

    • Author(s)
      Ogoh H, Kishimoto A, Suzuki M, Hara K, Tanga N, Tanuma N, Watanabe T andShima H
    • Organizer
      10th International Conference on Protein Phosphatase
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Final Research Report
  • [Presentation] Embryonic Lethality Caused in Mice Lacking the phosphatase domain of the PP6c gene2013

    • Author(s)
      Honami Ogoh
    • Organizer
      第10回プロテインホスファターゼ国際カンファレンス
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] リン酸化によるスフライシング装置タンハクSap155/Sf3b1制御機構2012

    • Author(s)
      島礼
    • Organizer
      日本プロテインホスファターゼ研究会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2012-01-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] PP6c遺伝子は胚の初期発生時期に必須である2012

    • Author(s)
      島礼
    • Organizer
      日本プロテインホスファターゼ研究会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2012-01-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] ピルビン酸キナーゼM(PKM)の発現アイソフォーム固定したマウスの作出2012

    • Author(s)
      田沼延公、岸本綾子、松本祥子、野村美有樹、近藤玄、国下侑里、片倉隆一、佐藤雅美、渡邊利雄、島礼
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] ピルビン酸キナーゼM2はダイオキシン受容体の活性化補助因子である2012

    • Author(s)
      松田俊、足立淳、井原賢、田沼延公、島礼、井倉正枝、井倉毅、松田知成
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] ワールブルグ効果に関するin vivo解析のためのマウスモデル開発2012

    • Author(s)
      松本祥子、岸本綾子、国下侑里、近藤玄、野村美有樹、渡邊利雄、島礼、田沼延公
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] ES細胞におけるピルビン酸キナーゼM(PKM)アイソフォームの機能解析‐ノックイン細胞を用いて2012

    • Author(s)
      田沼延公、岸本綾子、国下侑里、松本祥子、近藤玄、坂本良美、野村美有樹、渡邊利雄、島礼
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 悪性グリオーマ検体およびグリオーマ樹立株におけるPTPzetaの解析2012

    • Author(s)
      山下洋二、春日井勲、田沼延公、柴原一陽、園田順彦、金森政之、齋藤竜太、隅部俊宏、冨永悌二、島礼、片倉隆一
    • Organizer
      脳神経外科学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] PKMスイッチ不可能なマウスモデル2012

    • Author(s)
      田沼延公、渡邊利雄、野村美有樹、佐藤郁郎、椎葉健一、山下洋二、佐藤雅美、島礼
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] PP6触媒サブユニット遺伝子は、胚の初期発生時期に必須である2012

    • Author(s)
      渡邊利雄、田沼延公、島礼
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] ES細胞におけるピルビン酸キナーゼM(PKM)アイソフォームの機能解析‐ノックイン細胞を用いて2012

    • Author(s)
      田沼延公
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] ワールブルグ効果に関するin vivo解析のためのマウスモデル開発2012

    • Author(s)
      松本祥子
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] ピルビン酸キナーゼM(PKM)の発現アイソフォーム固定したマウスの作出2012

    • Author(s)
      田沼延公
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Embryonic Lethality Caused in Mice Lacking the phosphatase domain of the PP6c gene2011

    • Author(s)
      島礼
    • 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
    • Related Report
      2011 Annual Research Report
  • [Presentation] Protein Phosphatases in human Glioma Samples2011

    • Author(s)
      Shima H
    • Organizer
      The first Japan-Taiwan Bilateral Conference on Protein Phosphatases
    • Place of Presentation
      Okazaki
    • Year and Date
      2011-12-02
    • Related Report
      2012 Final Research Report
  • [Presentation] Protein Phosphatases in human Glioma Samples2011

    • Author(s)
      島礼
    • Organizer
      The First Japan-Taiwan Bilateral Conference on protein phosphatases
    • Place of Presentation
      岡崎(招待講演)
    • Year and Date
      2011-12-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] グリオーマにおけるピルビン酸キナーゼM(PKM)スプライシングのスイッチ機構2011

    • Author(s)
      島礼
    • Organizer
      第29回日本脳腫瘍学会学術集会
    • Place of Presentation
      下呂
    • Year and Date
      2011-11-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] グリオーマにおけるピルビン酸キナーゼM(PKM)スプライシングのスイッチ機構2011

    • Author(s)
      島礼
    • Organizer
      日本脳神経外科学会第70回学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-10-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Phospho-Regulation of Spliceosomal Protein, Sap155/Sf3b1.2011

    • Author(s)
      島礼
    • Organizer
      9^<th> International Conference on Protein Phosphatrase
    • Place of Presentation
      東京
    • Year and Date
      2011-02-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of Protein Phosphatases in Human Glioma Patients.2011

    • Author(s)
      島礼
    • Organizer
      9^<th> International Conference on Protein Phosphatrase
    • Place of Presentation
      東京
    • Year and Date
      2011-02-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] Embryonic Lethality Caused in Mice Lacking the phosphatase domain of thePP6c gene2011

    • Author(s)
      Kishimoto A, Tanuma N, Suzuki M, Sasaki, N Abe T, Kiyonari H, Aizawa S-i,Watanabe T, Shima H
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Switch of pyruvate kinase M (PKM) isoforms in human breast cancers2011

    • Author(s)
      野村美有樹、田沼延公、角川陽一郎、島礼
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Analysis of Protein Phosphatases in Human Glioma Samples2011

    • Author(s)
      Shima H
    • Organizer
      9th International Conference on Protein Phosphatase & Ist International Symposium on Carcinogenic Spiral
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Final Research Report
  • [Presentation] Phospho-Regulation of Splicesomal Protein, Sap155/Sf3b12011

    • Author(s)
      Tanuma N, Nomura M, Sato M, Yamashita Y, Shiiba K, Katakura K, and ShimaH
    • Organizer
      9th International Conference on Protein Phosphatase & Ist International Symposium on Carcinogenic Spiral
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Final Research Report
  • [Presentation] Conversion of pyruvate kinase M (PKM) isozymes in human canters-an analysis using isoform-specific antibodies2010

    • Author(s)
      島礼
    • Organizer
      BMB2010 第33回日本分子生物学会年会第83回日本生化学学会大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Drift of pyruvate kinase M (PKM) alternative splicing associating with Warburg effect in human cancers.2010

    • Author(s)
      島礼
    • Organizer
      BMB2010 第33回日本分子生物学会年会第83回日本生化学学会大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Conversion of pyruvate kinase M (PKM) isozymes in human cancers - an analysis using isoform-specific antibodies2010

    • Author(s)
      野村美有樹、田沼延公、佐々木希、島礼
    • Organizer
      BMB 2010 第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] Drift of pyruvate kinase M (PKM) alternative splicing associating with Warburg effect in human cancers2010

    • Author(s)
      田沼延公、野村美有樹、大内司、佐藤雅美、片倉隆一、島礼
    • Organizer
      BMB 2010 第33回日本分子生物学会年会、第83回日本生化学学会大会 合同大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] Generation of isoform-specific antibodies against pyruvate kinase (PKM)2010

    • Author(s)
      野村美有樹、田沼延公、山下洋二、椎葉健一、角川陽一郎、佐藤郁郎、島礼
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] Aberrant pre-mRNA splicing of pyrubate kinase M (PKM) in human cancer2010

    • Author(s)
      田沼延公、野村美有樹、山下洋二、椎葉健一、角川陽一郎、佐藤郁郎、島礼
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Book] 細胞工学「ホスファターゼ研究新章」2011

    • Author(s)
      島礼
    • Total Pages
      2
    • Publisher
      秀潤社
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.miyagi-pho.jp/mcc/kenkyu/yakubutsu.html

    • Related Report
      2012 Final Research Report

URL: 

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

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