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Proteomic analysis of the pathogenic domain related to aggregate formation

Research Project

Project/Area Number 15390279
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionRIKEN

Principal Investigator

NUKINA Nobuyuki  RIKEN, Molecular Neuropathology Group, Group Director, 病因遺伝子研究グループ, グループディレクター (10134595)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥10,000,000 (Direct Cost: ¥10,000,000)
Keywordsraft / polyglutamine / inclusion / aggregate / ubiquitin / Alzheimer disease / sodium channel beta subunit / P62 / プロテオミクス / ハンチントン病 / beta4 subunit / プロテオーム / ポリグルタミン病 / 質量分析 / p62 / aggresome
Research Abstract

We studied on the domain, which related to aggregate formation, especially on raft and polyglutamine aggregate itself. The followings are the results which we obtained in this projects.
1.The protein specific raft isolation method was established.
2.P62 was identified as a protein, which increased as the polyglutamine aggregates were formed.
3.We established isolation method of polyglutamine aggregate without using strong detergent and mass spectrometry analysis was performed to identify aggregate associated proteins(AIP). We found several known and unknown proteins in AIP including ubiquilin, one of the ubiquitin binding proteins.
4.We found sodium channel beta subunit 4 as a decrease protein in Huntington disease brain. The beta subunits exist in the raft fraction in the brain.
5.Beta subunits are identified as new substrates for both BACE1 and gamma secretase.
6.We made transgenic mouse of huntingtin exon1 fused with EGFP to visualize the aggregates.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] Decreased expression of hypothalamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine-EGFP fluorescent aggregates.2005

    • Author(s)
      Kotliarova, S., Jana, N.R., Sakamoto, N.et al.
    • Journal Title

      J Neurochem 93

      Pages: 641-653

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] beta subunits of voltage-gated sodium channels are novel substrates of BACE1 and gamma-secretase.2005

    • Author(s)
      Wong, H.K., Sakurai, T., Oyama, F., et al.
    • Journal Title

      J Biol Chem (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] beta subunits of voltage-gated sodium channels are novel substrates of BACE1 and gamma-secretase.2005

    • Author(s)
      Wong, H.K., Sakurai, T., Oyama, F.et al.
    • Journal Title

      J Biol Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes.2005

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

      J Biol Chem

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of ubiquitin-interacting proteins in purified polyglutamine aggregates.2004

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

      FEBS Lett 571

      Pages: 171-176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins.2004

    • Author(s)
      Venkatraman, P.et al.
    • Journal Title

      Mol Cell 14

      Pages: 95-104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.2004

    • Author(s)
      Tanaka, M.et al.
    • Journal Title

      Nat Med 10

      Pages: 148-154

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins.2004

    • Author(s)
      Venkatraman, P. et al.
    • Journal Title

      Mol Cell 14

      Pages: 95-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.2004

    • Author(s)
      Tanaka, M. et al.
    • Journal Title

      Nat Med 10

      Pages: 148-154

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes.2004

    • Author(s)
      Vetrivel, K.S., et al.
    • Journal Title

      J Biol Chem 279

      Pages: 44945-44954

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular and functional analysis of Caenorhabditis elegans CHIP, a homologue of Mammalian CHIP.2004

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

      FEBS Lett 565

      Pages: 11-18

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins.2004

    • Author(s)
      Venkatraman, P., et al.
    • Journal Title

      Mol Cell 14

      Pages: 95-104

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.2004

    • Author(s)
      Tanaka, M., et al.
    • Journal Title

      Nat Med 10

      Pages: 148-154

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway.2004

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

      J Biol Chem 279

      Pages: 11680-11685

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pro-apoptotic protein kinase C delta is associated with intranuclear inclusions in a transgenic model of Huntington's disease.2003

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

      J Neurochem 87

      Pages: 395-406

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pro-apoptotic protein kinase C delta is associated with intranuclear inclusions in a transgenic model of Huntington's disease.2003

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

      J Neurochem 87

      Pages: 395-406

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Tanaka, M. et al.: "Trehalose effectively alleviates polyglutamine-mediated pathology in a transgenic mouse model of Huntington's disease"Nat Med. 10. 148-154 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zemskov, E.A. et al.: "Pro-apoptotic protein kinase C delta is associated with intranuclear inclusions in a transgenic model of Huntington's disease"J Neurochem. 87. 395-406 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zemskov, E.A. et al.: "Impaired degradation of PKCalpha by proteasome in a cellular model of Huntington's disease"Neuroreport. 14. 1435-1438 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwata, A. et al.: "Alpha-synuclein degradation by serine protease neurosin : implication for pathogenesis of synucleinopathies"Hum Mol Genet. 12. 2625-2635 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka, M. et al.: "Expansion of polyglutamine induces the formation of quasi-aggregate in the early stagee of protein fibrillization"J Biol Chem. 278. 34717-34724 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Park, T.J.et al.: "Inhibition of ubiquitin ligase Siah-1A by disabled-1"Biochem Biophys Res Commun. 302. 671-678 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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