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Identification of the novel genes which regulated differentiation of neuronal tissues and the diseases caused by their defects

Research Project

Project/Area Number 10470296
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKumamoto University

Principal Investigator

SAYA Hideyuki  Kumamoto University, School of Medicine, Tumor Genetics & Biology, Professor, 医学部, 教授 (80264282)

Co-Investigator(Kenkyū-buntansha) ARAKI Norie  Kumamoto University, School of Medicine, Tumor Genetics & Biology, Instructor, 医学部, 助手 (80253722)
NAKAO Mitsuyoshi  Kumamoto University, School of Medicine, Tumor Genetics & Biology, Instructor, 医学部, 助手 (00217663)
MIMORI Tatsuyuki  Kumamoto University, School of Medicine, Tumor Genetics & Biology, Professor, 医学部, 助教授 (00117384)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1998: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsDrosophila / NE-dlg / p51-nedasin / 1(3)mbt / synapse / calmodulin / EST / Polycomb / DLG / NMDAレセプター / PDZドメイン / p51-nedasin / P-dlg
Research Abstract

1) NE-dlg is a human homologue of the Drosophila DLG. We found that NE-dlg binds to NMDA receptor subunit 2B at the synaptic membrane sites in neurons, and that their expressions increase in parallel with the onset of a synaptogenesis. NE-dlg was found to interact with PSD-95 in the presence of calmodulin and calcium and is speculated to regulate the clustering of NMDA receptors to form the synapses. Furthermore, we identified a novel cytoplasmic NE-dlg-interacting protein, termed p51-nedasin. We found that nedasin competitively inhibits the binding between the NMDA receptors and NE-dlg. These results suggest that nedasin modifies the dlg-related molecular clustering at the synaptic sites during development of neuronal cells.
2) Recessive mutations of the lethal (3)malignant brain tumor (D-1(3)mbt) gene result in malignant proliferation of the neuroblasts in the Drosophila larval brain. The structure of D-1(3)mbt protein is similar to sex comb on midleg (Scm) protein which is a member of Polycomb group (PcG) proteins. We isolated a human homolog of the 1(3)mbt gene, designated h-1(3)mbt. The h-1(3)mbt is expressed in most of the human normal tissues and cultured cell lines. The h-1(3)mbt protein shows a speckled and scattered distribution in interphase nuclei and localizes to condensed chromosomes in mitotic cells. Overexpression of h-1(3)mbt by a Cre-mediated gene activation system leads to failures of proper chromosome segregation and cytokinesis, which result in formation of multinuclei in U251MG cells. These observations suggest that h-1(3)mbt protein has functions distinct from those of PcG proteins and may play a role in proper progression of cell division.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Matsuko, N. et al.: "Interaction of NE-dlg/SAP102, a neural and endocrine tissue-specific MAGUK protein, with calmodulin and PSD-95/SAP90"J. Biol. Chem.. 274. 5782-5790 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuwahara, H. et al.: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and NMDA receptor"J. Biol. Chem.. 274. 32204-32214 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koga, H. et al.: "A human homolog of Drosophia lethal (3) malignant brain tumor (1(3)mbt) protein associates with condensed mitotic chromosomes"Oncogene. 18. 3799-3809 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto, I. et al.: "CD44 cleavage induced by a membrane-associated metalloprptease plays a critical role in tumor cell migration"Oncogene. 18. 1435-1446 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, H. et al.: "Identification of a novel human homolog of the Drosophila dlg, P-dlg, specifically the gland tissues and intereacted with p55"FEBS Letters. 433. 63-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto, I. et al.: "Regulated CD44 Cleavage Under the Control of Protein Kinase C, Calsium Influx and the Rho Family of Small G Proteins"J. Biol. Chem.. 274. 25525-25534 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura H, Sudo T, Tsuiki H, Miyake H, Morisaka T, Sasaki J, Masuko N, Kochi M, Ushio Y and Saya.H: "Identification of a novel human homolog of the Drosophila dlg, P-dlg, specifically expressed in the gland tissues and interacted with p55."FEBS Letters. 433. 63-67 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto I, Kawano Y, Matsumoto M, Suga M, Kaibuchi K,, Ando M, and Saya H: "Regulated CD44 Cleavage Under the Control of Protein Kinase C, Calcium Influx and the Rho Family of Small G Proteins."J Biol Chem. 274. 25525-25534 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi N, Tuiki H, Saya H, and Kaibuchi K: "Localization of the gene coding for ROCKII/Rho kinase on human chromosome 2p24"Genomics. 55. 235-237 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mugita N, Honda Y, Nakamura H, Fujiwara T, Tanaka K, Omura S, Shimbara N, Ogawa M, Saya H, and Nakao M: "The involvement of proteasome in myogenic differentiation of murine myocytes and human rhabdomyosarcoma cells"Int J Mol Med. 3. 127-137 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masuko N, Makino K, Kuwahara H, Fukunaga K, Sudo T, Araki N, Yamamoto H, Yamada Y, Miyamoto E and Saya H: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific MAGUK protein, with calmodulin and PSD-95/SAP90: a possible regulatory role in molecular clustering at synaptic sites"J Biol Chem. 274. 5782-5790 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koga H, Matsui S, Hirota T, Takebayashi S, Okumura K, and Saya H: "A human homolog of Drosophila lethal (3) malignant brain tumor (1(3)mbt) protein associates with condensed mitotic chromosomes"Oncogene. 18. 3799-3809 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujita N, Takebayashi S, Okumura K, Kudo S, Chiba T, Saya H and Nakao M: "Methylation-mediated transcriptional silencing in euchro-matin by methyl-CpG binding protein MBD1 isoforms"Mol Cell Biol. 19. 6415-6426 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata Y, Anan T, Yoshida T, Mizukami T, Taya Y, Fujiwara T, Kato H, Saya H and Nakao M: "The stabilization mechanism of mutant-type p53 by impaired ubiquitination: the loss of wild-type p53 function and the hsp90 association"Oncogene. 18. 6037-6049 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuwahara H, Araki N, Makino K, Masuko N, Honda S, Kaibuchi K, Fukunaga K, Miyamoto E, Ogawa M and Saya H: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP 102 and NMDA receptor"J Biol Chem. 274. 32204-32214 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S, Makino K, Yamamoto H, Hiraoka T, Kitamura N, and Saya H: "A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis"FEBS Letters. 459. 158-165 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito K, Okamoto I, Araki N, Kawano Y, Nakao M, Fujiyama S, Tomita K, Mimori T and Saya H: "Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of b-catenin from cell-cell contacts"Oncogene. 18. 7080-7090 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okaichi K, Wang LH, Sasaki J, Saya H, Tada M, and Okumura Y.: "A point mutation of human p53, which was not detected as a mutation by a yeast functional assay, led to apoptosis but not p21Waf1/Cip1/Sdi1 expression in response to ionizing radiation in a human osteosarcoma cell line, Saos-2"Int J Radiat Oncol Biol Phys. 45. 975-980 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto I, Kawano Y, Tsuiki H, Sasaki J, Nakao M, Suga M, Ando M, Nakajima M and Saya H: "CD44 cleavage induced by a mem-brane-associated metalloprotease plays a critical role in tumor cell migration"Oncogene. 18. 1435-1446 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masuko,N. et al.: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific MAGUK protein, with calmodulin and PSD-95/SAP90."J. Biol. Chem.. 274. 5782-5790 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuwahara,H. et al.: "A novel NE-dlg/SAP102-associated protein, P51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and NMDA receptor."J. Biol. Chem.. 274. 32204-32214 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koga,H. et al.: "A human homolog of Drosophila lethal (3) malignant brain tumor (I(3)mbt) protein associates with condensed mitotic chromosomes."Oncogene. 18. 3799-3809 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto,I. et al.: "CD44 cleavagc induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration."Oncogene. 18. 1435-1446 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto,I. et al.: "Regulated CD44 Cleavage Under the Control of Protein Kinase C, Calcium Influx and the Rho Family of Small G Proteins."J. Biol. Chem.. 274. 25525-25534 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito,K. et al.: "Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of β-catenin from cell-cell contacts."Oncogene. 18. 7080-7090 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,H.et al.: "Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region." Oncogene. 16. 1009-1019 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koga,H.et al.: "Impairment of cell adhesion by expression of the mutant neurofibromatosis-type 2 (NF2) genes which lack exons in the ERM-homology domain." Oncogene. 17401. 801-810 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kimura,Y.et al.: "The involvement of calpain-dependent proteolysis ofthetumor suppressor NF2 (merlin) in schwanpomas and meningiomas." Nature Medicine. 4. 915-922 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masuko,N.et al.: "Interaction of NE-dlg/SAP102,a neuronal and endocrine tissue-specific MAGUK protein,with calmodulin and PSD-95/SAP90" J.Biol.Chem.(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koga,H.et al.: "A human homolog of Drosophila lethal (3) malignant brain tumor (l(3)mbt) pro-tein associates with condensed mitotic chromosomes." Oncogene. (印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura,H.et al.: "Identification of a novel human homolog of the Drosophila dlg,P-dlg,specifically expressed in the gland tissues and interacted with p55." FEBS Letters. 433. 63-67 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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