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The regulation mechanism of degradation of p35 CDK5 activation subunit in neurons

Research Project

Project/Area Number 12680700
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HISANAGA Shin-ichi  Graduate School of Science, Professor, 理学研究科, 教授 (20181092)

Co-Investigator(Kenkyū-buntansha) SAITO Taro  Graduate School of Science, Research Assistant, 理学研究科, 助手 (70301413)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsNeuron / Cdk5 / proteasome / Calpain / phosphorylation / Neuronal cell death / CDK5 / 蛋白分解 / プロテインキナーゼ / 神経細胞 / 脳 / p35
Research Abstract

Cdk5, a cdc2-related kinase expressed in postmitotic neurons, is activated by association with a brain-specific activator, p35. It has been suggested that the conversion of p35 to p25 by the protease calpain is involved in neuronal cell death. On the other hand, p35 protein is rapidly turned over via proteasomal degradation in living neurons. Here, we show that the phosphorylation of p35 is involved in the control of its proteolytic degradation, and that the phosphorylation status of p35 changes in a developmental manner. The phosphorylated form of p35 is resistant to cleavage by calpain and is more susceptible to proteasomal degradation. The unphosphorylated form of p35 is more resistant to proteasomal degradation but is more susceptible to calpain-dependent cleavage to produce p25. Autophosphorylation of p35 by Cdk5 suppresses the cleavage to p25 by calpain, whereas autophosphorylation facilitates the proteasomal degradation of p35. A phosphorylated form of p35 is more prevalent in the fetal brain, whereas the unphosphorylated form of p35 occurs in the adult brain. These results suggest that the autophosphorylation of p35 serves as a protective mechanism that suppresses the generation of p25 in developing brains.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kitazawa et al.: "Ser787 in the proline-rich region of human MAP4 is a critical phosphorylation site that reduces the microtubule polymerization activity"Cell Struct Funct. 25. 33-39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokuoka et al.: "BDNF-induced phosphorylation of neurofilament-H subunit in primary culture of rat cortical neurons"J.Cell Science. 113. 1059-1068 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusakawa et al.: "Calpain-dependent proteolytic cleavage of the p35 CDK5 activtor to p25"J.Biol.Chem.. 275. 17166-17172 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniguchi et al.: "Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains"FEBS letter. 489. 46-50 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Bibb et al.: "Phosphorylation of protein phosphatase inhibitore-I by Cdk5"J.Biol.Chem.. 276. 14490-14497 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida et al.: "The neurofilament of Klotho, the mutant mouse prepaturely displaying symptoms resembling human aging"J.Neurosci.Res. 64. 364-370 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 久永眞市: "CDK5:分裂しない神経細胞で機能するCDK"実験医学(羊土社). 6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitazawa, H. et al.: "Ser787 in the proline-rich region of human MAP4 is a critical phosphorylation site that reduces the microtubule polymerization activity"Cell Struct. Funct.. 25. 33-39 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tokuda, H. et al.: "BDNF-induced phosphorylation of neurofilament-H subunit in primary culture of rat cortical neurons"J. Cell Sci.. 113. 1059-1068 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusakawa, G. et al.: "Calpain-dependent proteolytic cleavage of the p35 CDK5 activator to p25"J. Biol. Chem.. 275. 17166-17172 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniguchi, S. et al.: "Calpain-mediated degradation of p35 to p25 postmortem human and rat brains"FEBS letter. 489. 46-50 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Bibb, J. A. et al.: "Phosphorylation of protein phosphatase inhibitor-I by Cdk5"J. Biol. Chem.. 276. 14490-14497 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida, A. et al.: "The neurofilament of Klotho, the mutant mouse prepaturely displaying symptoms resembling human aging"J. Neurosci. Res.. 64. 364-370 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hisanaga, S.: "CDK5 : CDK functioning in post-mitotic neurons"Experimental Medicine, Yodo-sha. 18. 878-883 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Alim MA et al.: "Tubulin seeds a-synuclein fibril formation"J Biol Chem. 272. 2112-2117 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chang W et al.: "Phosphorylation of MAP4 affects microtubule properties and cell cycle progression"J Cell Sci. 114. 2879-2887 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bibb JA et al.: "Phosphorylation of protein phosphatase inhibitore-I by Cdk5"J Biol Chem. 276. 14490-14497 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchida A et al.: "The neurofilament of Klotho, the mutant mouse prepaturely displaying symptoms resembling human aging"J Neurosci Res. 64. 364-370 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi S et al.: "Calpain-mediated degradation of p35 to p25 in postmortem human and rat brains"EBBS letter. 489. 46-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 斎藤太郎 他: "神経細胞におけるCdk5、Cdk5の活性調節機構"生化学. 73. 276-278 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Bibb,J.: "Phosphorylation of protein phosphatase inhibitore-I by Cdk5.J."Biol.Chem.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchida,A.: "The neurofilament of Klotho, the mutant mouse prepaturely displaying symptoms resembling human aging."J.Neurosci,Res.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi,S.: "Calpain-mediated degadation of p35 to p25 in postmortem human and rat brains."FEBS letter. 489. 46-50 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kusakawa,G.: "Calpain-dependent proteolytic cleavage of the p35 CDK5 activtor to p25."J.Biol.Chem.. 275. 17166-17172 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitazawa,H.: "Ser787 in the proline-rich region of human MAP4 is a critical phosphorylation site that reduces the microtubule polymerization activity."Cell Struct.Funct.. 25. 33-39 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokuoka,H.: "BDNF-induced phosphorylation of neurofilament-H subunit in primary culture of rat cortical neurons."J.Cell Sci.. 113. 1059-1068 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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