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Characterization of a novel kinetochore protein that are involved in cell growth and differentiation.

Research Project

Project/Area Number 17590980
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

KAWASHIMA Toshiyuki  The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (10306839)

Co-Investigator(Kenkyū-buntansha) KITAMURA Toshio  The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (20282527)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordskinetochore / CENP / cytokinesis / GAP / sister chromosome / microtubules / two-hybrid / ツーハイブリッド法
Research Abstract

Our group previously showed that a GTPase activating protein, MgcRacGAP, plays critical roles both in cellular differentiation and cytokinesis (Kawashima et al.,Blood,2000:Hirose et al.,J.Biol.Chem.,2001:Minoshima et al.,Dev.Cell,2003:Tonozuka et al.,Blood 2004:Kawashima et al.,J.Cell.Biol.,2006). In the present study, we identified a protein that interacts with MgcRacGAP by yeast two-hybrid screening. Because this protein localizes to the centromere throughout the cell cycle, we named it CENP-50 (CENtromere Protein, molecular weight 50 KDa). Recently, CENP-50 was also described as KLIP1/MLF1IP. We identified CENP-50 as a novel kinetochore component. We found that CENP-50 is a constitutive component of the centromere that colocalizes with CENP-A and CENP-H throughout the cell cycle in vertebrate cells. To determine the precise role of CENP-50, we examined its role in centromere function by generating a loss-offunction mutant in the chicken DT40 cell line. The CENP-50 knockout was not l … More ethal ; however, the growth rate of cells with this mutation was slower than that of wild-type cells. We observed that the time for CENP-50-deficient cells to complete mitosis was longer than that for wild-type cells. Centromeric localization of CENP-50 was abolished in both CENP-H- and CENP-I-deficient cells. Co-immunoprecipitation experiments revealed that CENP-50 interacted with the CENP-H/CENP-I complex in chicken DT40 cells. We observed severe mitotic defects in CENP-50-deficient cells with apparent premature sister chromatid separation when the mitotic checkpoint was activated, indicating that CENP-50 is required for recovery from spindle damage. Observed premature sister chromatid separation in CENP-50-deficient cells suggested that CENP-50 is required for maintenance of sister chromatid adhesion (Minoshima et al.,Mol.Cell.Biol.,2005). In addition, we have recently identified the region of CENP-50 required for localization to the centromere, and did functional analysis of this region (manuscript in preparation). Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (35 results)

All 2006 2005 Other

All Journal Article (35 results)

  • [Journal Article] Integrin aIIbb3 induces the adhesion and activation of mast cells through interaction with fibrinogen.2006

    • Author(s)
      Oki, T et al.
    • Journal Title

      J. Immunol. 176

      Pages: 52-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

    • Author(s)
      Nakajima, H et al.
    • Journal Title

      Int. J. Hematol. 84

      Pages: 54-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPa.2006

    • Author(s)
      Fukuchi, Y et al.
    • Journal Title

      EMBO J. 25

      Pages: 3398-3410

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Rac1 and a GTPase activating protein MgcRacGAP are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      Kawashima. T et al.
    • Journal Title

      J. Cell Biol. 175

      Pages: 937-946

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Integrin aIIbb3 induces the adhesion and activation of mast cells through interaction with fibrinogen.2006

    • Author(s)
      Oki, T, et al.
    • Journal Title

      J.Immunol. 176

      Pages: 52-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

    • Author(s)
      Nakajima, H, et al.
    • Journal Title

      Int.J.Hematol. 84

      Pages: 54-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPa.2006

    • Author(s)
      Fukuchi, Y, et al.
    • Journal Title

      EMBO J. 25

      Pages: 3398-3410

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Rac1 and a GTPase activating protein MgcRacGAP are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      Kawashima, T, et al.
    • Journal Title

      J.Cell.Biol. 175

      Pages: 937-946

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] integrin aIIbβ3 induces the adhesion and activation of mastcells through interaction with fibrinogen.2006

    • Author(s)
      沖 俊彦
    • Journal Title

      J. Immunol. 176

      Pages: 52-60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immune supperssor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells.2006

    • Author(s)
      中島 秀明
    • Journal Title

      Biochem. Biophys. Res. commun. 340

      Pages: 35-42

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

    • Author(s)
      中島 秀明
    • Journal Title

      Int. J. Hematol. 84

      Pages: 54-59

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBpα.2006

    • Author(s)
      福地 由美
    • Journal Title

      EMBO J. 25

      Pages: 3398-3410

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Racl and a GTPase activating protein MgcRacGAP are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      川島 敏行
    • Journal Title

      J. Cell Biol. 175

      Pages: 937-946

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen2006

    • Author(s)
      沖俊彦
    • Journal Title

      J.Immunol. 176

      Pages: 52-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells2006

    • Author(s)
      中島秀明
    • Journal Title

      Biochem.Byiophys.Res.Commun. 印刷中

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis.2005

    • Author(s)
      Ono, R et al.
    • Journal Title

      J. Clin. Invest. 115

      Pages: 919-929

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ect-2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F et al.
    • Journal Title

      J. Cell Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia.2005

    • Author(s)
      Urano, A, et al.
    • Journal Title

      Mol. Cell. Biol. 15

      Pages: 6834-6845

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective activation of STAT5 unveils its role in stem cell self-renewal of normal and leukemic hematopoiesis.2005

    • Author(s)
      Kato, Y, et al.
    • Journal Title

      J. Exp. Med. 202

      Pages: 169-179

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human leukemias with mutated FLT3 kinase are sinergistically sensitive to FLT3 and Hsp90 inhibitors : the key role of the STAT5 signal transduction pathway.2005

    • Author(s)
      Yao, R, et al.
    • Journal Title

      Leukemia 19

      Pages: 1605-1612

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage.2005

    • Author(s)
      Minoshima, Y et al.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 10315-10328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Disruption of Sept6, a fusion partner gene of Mixed Lineage Leukemia (MLL), does not affect the ontogeny, leukemogenesis induced by MLL-SEPT6, or the phenotype induced by the loss of Sept4.2005

    • Author(s)
      Ono, R et al.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 10965-10978

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pen-2 is incorporated into the g-secretase complex through binding to transmembrane domain 4 of presenilin 1.2005

    • Author(s)
      Watanabe, N et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dimerization of MLL fusion protein and FLT3 activation synergize to induce multiple lineage leukemogenesis.2005

    • Author(s)
      Ono, R, et al.
    • Journal Title

      J.Clin.Invest. 115

      Pages: 919-929

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ect-2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Pceguera-Yanez, F, et al.
    • Journal Title

      J.Cell.Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infertility with defective spermigenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia.2005

    • Author(s)
      Urano, A, et al.
    • Journal Title

      Mol.Cell.Biol. 15

      Pages: 6834-6845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective activation of STAT5 unveils its role in stem cell self-renewal of normal and leukemic hematopoiesis.2005

    • Author(s)
      Kato, Y, et al.
    • Journal Title

      J.Exp.Med. 202

      Pages: 269-179

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage.2005

    • Author(s)
      Minoshima, Y, at al.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10315-10328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Disruption of Sept6, a fusion partner gene of Mixed Lineage Leukemia (MLL), does not affect the ontogeny, leukemogenesis induced by MLL-SEPT6, or the phenotype induced by the loss of Sept4.2005

    • Author(s)
      Ono, R, et al.
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10965-10978

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pen-2 is incorporated into the g-secretase complex through binding to transmembrane domain 4 of presenilin 1.2005

    • Author(s)
      Watanabe, N, et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis2005

    • Author(s)
      小埜良一
    • Journal Title

      J.Clin.Invest. 115

      Pages: 919-929

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia2005

    • Author(s)
      浦野敦司
    • Journal Title

      Mol.Cell.Biol. 15

      Pages: 6834-6845

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage2005

    • Author(s)
      箕嶋幸範
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10315-10328

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disruption of Sep6, a fusion partner gene of Mixed Lineage Leukemia(MLL), does not affect the ontogeny, Leukemogenesis induced by MLL-SEPT6, or the phenotype induced by the loss of Sept42005

    • Author(s)
      小埜良一
    • Journal Title

      Mol.Cell.Biol. 280

      Pages: 10965-10978

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Functional analysis of an activating receptor LMIR4 as a counterpart of an inhibitory receptor LMIR3.

    • Author(s)
      伊沢 久末
    • Journal Title

      J. Biol. Chem. (In press.)

    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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