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Regulatory mechanisms of neuronal differentiation and death by necdin

Research Project

Project/Area Number 12480230
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

YOSHIKAWA Kazuaki  Osaka University, Institute for Protein Research, Professor, たんぱく質研究所, 教授 (30094452)

Co-Investigator(Kenkyū-buntansha) UETSUKI Taichi  Osaka University, Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (20260309)
TANIURA Hideo  Osaka University, Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (80263325)
NIINOBE Michio  Osaka University, Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (80135748)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥13,000,000 (Direct Cost: ¥13,000,000)
KeywordsNecdin / Neurons / Terminal differentiation / Apoptosis / Nuclear Matrix / Transcription repressor / E2F / Cell cycle / 細胞分裂終了 / 神経幹細胞 / 分化 / 細胞死 / ゲノムインプリンティング
Research Abstract

Necdin is expressed in terminally differentiated neurons, and enforced expression of this protein suppresses cell growth. Necdin binds to the transcription factors E2F1 and p53, both of which are involved in neuronal apoptosis, and suppresses their activities. Recently necdin is thought to be a candidate gene for Prader-Willi syndrome, a genomic imprinting-associated neurobehavioral syndrome. Therefore, necdin may be a pivotal factor that controls terminal differentiation and apoptosis in neurons. In this study, we analyzed the molecular interactions between necdin and its target proteins to gain insights into molecular background behind neuronal terminal differentiation and apoptosis. The results obtained are : 1) We isolated two cDNAs encoding proteins that interacts with necdin by yeast two-hybrid assay. One is the cytoplasmic calcium binding protein NEFA, and the other is the nuclear matrix protein hnRNP U. 2) NEFA is localized to the cytoplasm and endoplasmic reticulum, and regulates calcium metabolism in cooperation with necdin. 3) Both necdin and hnRNP U are localized to nuclear matrix and form a complex to suppress cell growth. 4) Necdin is abundant in the cytosol in differentiated neurons. 5) Necdin binds to specific G-rich motif and functions as a transcription repressor. These results suggest that necdin is involved in neuronal terminal differentiation and survival by interacting with various protein present in neuronal nucleus and cytoplasm.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Yoshikawa K: "Cell cycle regulators in neural stem cells and postmitotic neurons"Neuroscience Research. 37. 1-14 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniguchi N et al.: "The postmitotic growth suppressor necdin interacts with a calcium-binding protein (NEFA) in neuronal cytoplasm"Journal of Biological Chemistry. 275. 31674-31681 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakada Y et al.: "Characterization and chromosomal mapping of a human necdin pseudogene"Gene. 245. 185-191 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niinobe M et al.: "Cellular and subcellular localization of necdin in fetal and adult mouse brain"Developmental Neuroscience. 22. 310-319 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto K et al.: "Necdin acts as a transcriptional repressor that interacts with multiple guanosine clusters"Gene. 272. 173-179 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniura H, Yoshikawa K: "Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix"Journal of Cellular Biochemistry. 84. 545-555 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshikawa K: "Cell cycle regulators in neural stem cells and postmitotic neurons"Neuroscience Research. 37. 1-14 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniguchi N et al: "The postmitotic growth suppressor necdin interacts with a calcium-binding protein (NEFA) in neuronal cytoplasm"Journal of Biological Chemistry. 275. 31674-31681 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakada Y et al.: "Characterization and chromosomal mapping of a human necdin pseudogene"Gene. 245. 185-191 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niinobe M et al: "Cellular and subcellular localization of necdin in fetal and adult mouse brain"Developmental Neuroscience. 22. 310-319 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto K et al.: "Necdin acts as a transcriptional repressor that interacts with multiple guanosine clusters"Gene. 272. 173-179 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniura H and Yoshikawa K: "Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix"Journal of Cellular Biochemistry. 84. 545-555 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumoto K et al.: "Necdin acts as a transcriptional repressor that interacts with multiple guanosine clusters"Gene. 272. 173-179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniura H, Yoshikawa K: "Necdin, a postmitotic growth suppressor"Recent Res.Devel.Neurochem. 4. 67-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniura H, Yoshikawa K: "Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix"Journal of Cell Biochemistry. 84. 545-555 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakada Y et al.: "Characterization and chromosomal mapping of a human necdin pseudogene"Gene. 245. 185-191 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niinobe M et al.: "Cellular and subcellular localization of necdin in fetal and adult mouse brain"Developmental Neuroscience. 22. 310-319 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi N et al.: "The postmitotic growth suppressor necdin interacts with a calcium-binding protein (NEFA) in neuronal cytoplasm."Journal of Biological Chemistry. 275. 31674-31681 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshikawa K: "Cell cycle regulators in neural stem cells and postmitotic neurons"Neuroscience Research. 37. 1-14 (2000)

    • Related Report
      2000 Annual Research Report

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

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