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2004 Fiscal Year Final Research Report Summary

Role of a multifunctional protein Id2 in the control of cellular differentiation and function

Research Project

Project/Area Number 15390102
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionUniversity of Fukui (2004)
福井医科大学 (2003)

Principal Investigator

YOKOTA Yoshifumi  University of Fukui, Department of Molecular Genetics, Professor, 医学部, 教授 (50222386)

Co-Investigator(Kenkyū-buntansha) KUROOKA Hisanori  University of Fukui, Department of Molecular Genetics, Associate Professor, 医学部, 助教授 (00293879)
Project Period (FY) 2003 – 2004
Keywordstranscription factor / Id2 / cell differentiation / growth control / mammary epithelial cells / hydronephrosis / intracellular localization / 細胞内局在
Research Abstract

1.Id2 KO mice develop intestinal tumors in the middle portion of the ileum, showing a variety of the pathological grade. Immunohistochemical analysis demonstrates no enhanced expression and no nuclear localization of β-catenin protein. Smad4, a transcription factor that mediates the TGF β signaling, was detected similar to the normal tissue, while Cdx2 was absent in the tumors. We are continuing to study the mechanisms underlying the tumor formation in Id2 KO mice.
2.Id2 protein was found to shuttle between the nucleus and the cytoplasm. The nuclear localization of the protein was dependent on the basic amino acid residues in the helix-loop-helix region. The nuclear export signal was found in the C-terminal region and the export was dependent on CRM1. In the steady state, the nuclear export of Id2 protein was stronger than the nuclear import.
3.Id2 KO mice share the lactation defect phenotype with C/EBP β KO mice. We identified Id2 as a direct target of with C/EBP β. In addition to in vitro analyses, we demonstrated that the induction of Id2 gene expression is not observed in the pregnant mammary gland of C/EBP β KO mice.
4.The population of CD8+ T cells in the spleen is reduced in Id2 KO mice. We found that the expression of cyclin-dependent kinase inhibitors such as p21 and p27 is elevated at the protein level in Id2-deficient CD8+ T cells.
5.Id2 KO mice are hyperactive due to the increased release of dopamine in the striatum. We failed to detect any significant difference in the numbers and localization of GABAergic neurons in pars reticulata of substantia nigra.
6.We found that Id2 KO mice develop congenital hydronephrosis due to the stenosis at the ureteropelvic junction. Observed characteristics of hydronephrosis in the mutant mice were similar to those in human cases. Furthermore, Id2 haploinsufficiency also caused the malformation. Therefore, it was strongly suggested that Id2 is a candidate gene responsible for the development of congenital hydronephrosis.

  • Research Products

    (17 results)

All 2005 2004

All Journal Article (17 results)

  • [Journal Article] CpG inhibits IgE class switch recombination through suppression of NF-κB and Irf4 activity, but not through Id2 or Bcl6.2005

    • Author(s)
      Kusunoki T. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 328

      Pages: 499-506

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-loop-helix transcription factors.2005

    • Author(s)
      Kurooka H., Yokota Y.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 4313-4320

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of Id2 expression by CCAAT/enhancer binding protein β.2005

    • Author(s)
      Karaya K. et al.
    • Journal Title

      Nucleic acids Res. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-loop-helix transcription factors.2005

    • Author(s)
      Kurooka, H., Yokota, Y.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 4313-4320

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CpG inhibits IgE class switch recombination through suppression of NF-κB and Irf4 activities, but not through Id2 or Bcl6.2005

    • Author(s)
      Kusunoki, T. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 328

      Pages: 499-506

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of Id2 expression by CCAAT/enhancer binding protein β.2005

    • Author(s)
      Karaya, K. et al.
    • Journal Title

      Nucleic Acids Res. 33

      Pages: 1924-1934

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Accessibility control of recombination at immunoglobulin locus.2005

    • Author(s)
      Sugai, M. et al.
    • Journal Title

      Curr.Immunol.Rev. 1

      Pages: 69-79

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impaired IgG production in mice deficient for heat shock transcription factor 1.2004

    • Author(s)
      Inouye S. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 38701-38709

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans.2004

    • Author(s)
      Aoki Y.et al.
    • Journal Title

      Genes to Cells 9

      Pages: 1287-1296

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Id2 is dispensable for Myc-induced lymphomagenesis.2004

    • Author(s)
      Nilsson J.A. et al.
    • Journal Title

      Cancer Res. 64

      Pages: 7296-7301

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impairment of intestinal intraepithelial lymphocytes in Id2 deficient mice.2004

    • Author(s)
      Kim, J.-K.et al.
    • Journal Title

      Gut 53

      Pages: 480-486

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intestinal villous bacteria translocation islands : a new antigen entry site in the mucosal epithelium.2004

    • Author(s)
      Jang, M.H.et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 20

      Pages: 6110-6115

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impaired IgG production in mice deficient for heat shock transcription factor 1.2004

    • Author(s)
      Inouye, S. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 38701-38709

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans.2004

    • Author(s)
      Aoki, Y. et al.
    • Journal Title

      Genes to Cells 9

      Pages: 1287-1296

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Id2 is dispensable for Myc-induced lymphomagenesis.2004

    • Author(s)
      Nilsson, J.A. et al.
    • Journal Title

      Cancer Res. 64

      Pages: 7296-7301

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Wnt1 expression is epistatic to Id2 in modeling mammary gland development and in causing mammary tumors.2004

    • Author(s)
      Marino, S. et al.
    • Journal Title

      BMC Cancer 4

      Pages: 91

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of Id proteins in B cell activation : new insights from knockout mouse studies.2004

    • Author(s)
      Sugai, M. et al.
    • Journal Title

      J.Mol.Med. 82

      Pages: 592-599

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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