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Functional analysis of DAN and DA41 proteins in early embryogenesis

Research Project

Project/Area Number 10680658
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionChiba Cancer Center Research Institute

Principal Investigator

OZAKI Toshinori  Chiba Cancer Center Research Institute, 研究局・生化学研究部, 研究員 (40260252)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsBMP4 / DA41 / DAN / Growth suppression / DA41 / BMP2 / 分泌蛋白質
Research Abstract

(A) Functional analysis of DAN
Northern blot analysis revealed that the expression of DAN was significantly down-regulated in human osteosarcoma cell line SAOS-2. Overexpression of DAN in SAOS-2 resulted in a massive growth suppression as demonstrated by colony formation assays. N-terminal truncated form of DAN did not exhibit the growth suppressive activity, indicating that the secreted form of DAN is active. Reporter gene assay demonstrated that DAN inhibited the BMP4 signaling in mouse embryonic carcinoma P19 cells. These observations suggest that DAN, as well as Cerberus and Gremlin, may function as an antagonist against BMP in fog embryos and mammalian cells.
(B) Characterization of DA41
Ectopic overexpression of rat DA41 in V-Ha-ras-transformed 3Y1 cells (ras-3Y1) resulted in a significant growth suppression, which was associated with a remarkable reduction of CDK2 activity. Fluorescence in situ hybridization revealed that DA41 was mapped to human chromosome 9q21.2-q21.3, a position overlapping the candidate tumor suppressor locus for bladder cancer. Data base search for DA41-related proteins(s) identified mouse PLIC-1, PLIC-2, frog XDRP1, and yeast DSK2. It has been shown that XDRP1 inhibited the degradation of cyclin A and blocked the cell division. These observations suggest that DA41 and XDRP1 could share the similar function in the cell cycle regulation.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Nakamura, Y., Ozaki, T. et al.: "Ectopic expression of DAN enhances the trtinoic acid-induced neuronal differentiation in human neuroblastoma cell lines"Biochem. Biophys. Res. Commun.. 243. 711-726 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiwasa, T., Ozaki, T. et al.: "Down-regulation of protein kinase Cα and γand enhances TPA-induced neurite formation in DAN-transfected neuroblastoma cells"FEBS Lett.. 440. 25-28 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shishikura, T., Ozaki, T. et al.: "Mutational analysis of the p73 gene in human breast cancers"Int. J. Cancer. 84. 321-325 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takada, N., Ozaki, T. et al.: "Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas"Cancer Res.. 59. 2810-2814 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ozaki, T., Naka, M. et al.: "Deletion of the COOH-terminal region of p73 α enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Res.. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hanaoka, E., Ozaki T. et al.: "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3"J.hum. Genet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, Y., Ozaki, T. et al.: "Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines."Biochem. Biophys. Res. Commun.. 243. 722-726 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiwasa, T., Ozaki, T. et al.: "Down-regulation of protein kinase Cα and γ and enhanced TPA-induced neurite formation in DAN-transfected neuroblastoma cells."FEBS Lett.. 440. 25-28 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shishikura, T., Ozaki, T. et al.: "Mutational analysis of the p73 gene in human breast cancers."Int. J. Cancer. 84. 321-325 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takada, N., Ozaki, T. et al.: "Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas."Cancer Res.. 59. 2810-2814 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ozaki, T., Naka, M. et al.: "Deletion of the COOH-terminal region of p73α enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells."Cancer Res.. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hanaoka, E., Ozaki, T. et al.: "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3."J. Hum. Genet.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shishikura T.,Ozaki T.et al.: "Mutational analysis of the p73 gene in human breast cancers"Int.J.Cancer. 84. 321-325 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takada N.,Ozaki T.et al.: "Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas"Cancer Res.. 59. 2810-2814 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ozaki T.,Naka M.et al.: "Deletion of the COOH-terminal region of p73 α enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Res.. 59. 5902-5907 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hanaoka E.,Ozaki T.et al.: "Molecular cloning and expression analysis of the human DA41 gene and its mapping to chromosome 9q21.2-q21.3"J.Hum.Genet.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagai M.,Ozaki T.et al.: "Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2"Int.J.Oncol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,Y.,Ozaki,T.et al.: "Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines." Biochem.Biophys.Res.Commun.243. 722-726 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hishiki,T.,Ozaki,T.et al.: "GDNF/NTN-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret,GFRα-1 and GFRα-2." Cancer Res.58. 2158-2165 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uchimura,K.,Ozaki,T.et al.: "Human N-acetylglucosamine-6-0-sulfotransferase involved in the biosynthesis of 6-sulfo sialyl lewis X: Molecular cloning,chromosomal mapping,and expression in various organs and tumor cells." J.Biochem.124. 670-678 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiwasa,T.,Ozaki,T.et al.: "Down-regulation of protein kinase Cα and γ and enhanced TPA-induced neurite formation in DAN-transfected neuroblastoma cells." FEBS Lett.440. 25-28 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomita,S.,Ozaki,T.et al.: "Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein." J.Biol.Chem.274. 2243-2254 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ozaki,T.,Hanaoka,E.et al.: "Cloning and characterization of rat BAT3 cDNA." DNA Cell Biol.(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2017-10-12  

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