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Molecular cell-biological studies on differentiation and mitotic arrest of brain neurons

Research Project

Project/Area Number 08458253
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  Institute for Protein Research, Professor, たんぱく質研究所, 教授 (30094452)

Co-Investigator(Kenkyū-buntansha) UETSUKI Taichi  Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (20260309)
TANIURA Hideo  Institute for Protein Research, Instructor, たんぱく質研究所, 助手 (80263325)
NIINOBE Michio  Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (80135748)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsNecdin / Neurons / Cell differentiation / Retinoblastoma protein / Cell cycle / E2F1 / Prader-Willi syndrome / Genomic imprinting / がん抑制遺伝子 / プラダー・ウイリ症候群 / necdin / 胚性がん細胞 / 核蛋白質 / アデノウィルスベクター / 神経分化
Research Abstract

Neurons in the vertebrate central nervous system CNS withdraw permanently from the cell cycle immediately after differentiation from their proliferative progenitors. To study the molecular mechanism whereby neurons become postmitotic, we focused on the functional roles and molecular properties of necdin, a neuronal growth suppressor isolated from embryonal carcinoma P19 cells. Results obtained are as follows. [1] Necdin, like retinoblastoma protein (Rb), bound to transforming domains of simian virus 40 (SV40) large T antigen and adenovirus E1A.[2] Necdin bound to E2F-1, a cellular transcription factor that promotes the cell cycle, and suppressed its functions. [3] Ectopic expression of necdin in Rb-dificient SAOS-2 cells suppressed the cell growth, indicating that necdin is a functional substitute for Rb. [4] An antibody against recombinant necdin protein reacted with necdin in the cytoplasm of mouse brain neurons, and the immunoreactivity was the highest in the hypothalamus.[5] The 5'-end sequence of the human necdin gene contains frequent CpG dinucleotides (identified as a CpG island), and methylation in vitro of CpG dinucleotides in the promoter region suppressed the transcriptional activity. [6] The human necdin gene was localized to chromosome 15q11.2-q12, which lies within the region involved in Prader-Willi syndrome, a genomic imprinting-associated neurobehavioral disorder. [7] In summary, necdin suppresses cell growth in a manner similar to that of Rb, and its deficiency may cause the defect of neuronal differentiation.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Tominaga K, 他3名: "Glutamate responsiveness enhanced in neurons expressing amyloid precursor protein." NeuroReport. 8. 2067-2072 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taniura H.他3名: "Necdin,a postmitotic neuron-specific growth suppressor,interacts with viral transforming proteins and cellular transcription factor E2F1." Journal of Biological Chemistry. 273. 720-728 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishimura I.他7名: "Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer." Journal of Neuroscience. 273. 720-728 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 吉川 和明: "神経生物学のための遺伝子導入発現研究法" シュプリンガー・フェアラーク東京, 363 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga K,Uetsuki T,Ogura A,Yoshikawa K: "Glutamate responsiveness enhanced in neurons expressing amyloid precursor protein." NeuroReport. 8. 2067-2072 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa K: "Internal disintegration of neurons by amyloid beta protein precursors." In : Principles of Neural Aging (Dani S.U., Hori A.and Walter G.F.) Amsterdam : Elsevier. 115-125 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taniura H.Taniguchi N,Hara M,Yoshikawa K: "Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1." Journal of Biological Chemistry. 273. 720-728 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishimura I,Uetsuki T,Dani SU,Ohsawa Y,Saito I,Okamura H,Uchiyama Y,Yoshikawa K: "Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer." Journal of Neuroscience. 18. 2387-2398 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga,K.他3名: "Glutamate responsiveness enhanced in neurons expressing amyloid precursor protein." NeuroReport. 8. 2067-2072 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taniura,K.他3名: "Necdin,a postmitotic neuron-specific growth suppressor,interacts with viral transforming proteins and cellular transcription factor E2F1." Journal of Biological Chemistry. 273. 720-728 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishimura,I.他7名: "Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer." Journal of Neuroscience. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 吉川和明: "神経生物学のための遺伝子導入発現研究法" シュプリンガー・フェアラーク東京, 363 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uetsuki,T.,Takagi,K.Sugiura,H.,Yoshikawa,K.: "Structure and expression of the mouse necdin gene : Identification of a postmitotic neuron-restrictive core promoter" J.Biol.Chem.271. 918-924 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 吉川和明: "アルツハイマー病による神経細胞死" Molecular Medicine. 33. 160-166 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshikawa,K.: "Internal disintegration of neurons by amyloid beta protein precursor" Principles of Neural Aging. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 吉川和明: "神経生物学のための遺伝子導入発現研究法" シュプリンガーフェアラーク社,東京, 363 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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