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2000 Fiscal Year Final Research Report Summary

ABNORMAL RECOMBINATION ACTIVATING GENE (RAG) AND IMMUNO DEFICIENCY

Research Project

Project/Area Number 11470169
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

MURAGUCHI Atsushi  TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, PROFESSOR, 医学部, 教授 (20174287)

Co-Investigator(Kenkyū-buntansha) NAGATA Takuya  TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (40303242)
MATSUDA Tadashi  TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20212219)
KISHI Hiroyuki  TOYAMA MED AND PHAR.UNIV., FAC.OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60186210)
Project Period (FY) 1999 – 2000
KeywordsANTIGEN RECEPTOR GENE / GENE REARRANGEMENT / RAG / GENOMIC STRUCTURE / TRANSCRIPTIONAL REGULATION / PROMOTER / TARANSCRIPTIONAL FACTOR
Research Abstract

1. Human Rag genomic locus ; Using a fragment of human RAG-1 cDNA, we isolated genomic DNA clones that contained either first or second exon of human RAG-1. We determined its exon/intron organization and the transcriptional start site. Similarly, we isolated genomic DNA clones that contains first or second exon of human RAG-2 and determined its exon/intron structure and the transcription initiation site for RAG-2. These led us to reveal, for the first time, the organization of human genomic RAG-1 and RAG-2 locus.
2. Regulation of human RAG transcription ; We characterized promoter regions for human RAG-1 and RAG-2, and revealed that the 5' promoter region of RAG-lwas indispensable for its basal promoter activity. On the contrary, the sequences between -63 to -107 of RAG-2 were shown to be essential for its promoter acticity, suggesting the regulation of RAG-1 and RAG-2 transcription may be controled by different transcriptional mechanisms.
3. Regulation of murine RAG-2 ; We found that the regulation of the mouse RAG-2 promoter activity is confered to 80 nucleotide upstream of RAG-2. We also found that a B cell-specific transcription protein, Pax-5, and a T cell-specific transcription protein, GATA-3, bind to the -80 to -17 nt region in B cells and T cells, respectively. These results indicate that distinct DNA binding proteins, Pax-5 and GATA-3, may regulate the murine RAG-2 promoter in B and T lineage cells, respectively.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Tong,J.-J. et al: "Co-ordinate expression of pre-T-cell receptor complex and novel immature thymocyte-specific antigen during thymocyte development."Immunology. 96. 48-56 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasukawa,H. et al: "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop."The EMBO Journal. 18. 1309-1320 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tong,J.-J. et al: "A bone marrow-derived stroma cell line, ST2, can support the differentiation of fetal thymocytes from the CD4CD8^- double negative to the CD4^+CD8^+ double positive defferentiation stage in vitro."Immunology. 97. 672-678 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kish,H. et al: "Lineage-specific regulation of the murine RAG-2 promoter : GATA-3 in T cells and Pax-5 in B cells."Blood. 95. 3845-3852 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawakami,T. et al: "Alteration of protein composition in mouse thymocytes by signals through T-cell receptor."Electrophoresis. 21. 1846-1852 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuda,T. et al: "SOCS-1 can suppress CD3ζ-and Syk-mediated NF-AT activation in a non-lymphoid cell line."FEBS Letters. 472. 235-240 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata,T. et al: "Possible involvement of cyclophilin B and caspase-activated deoxyribonuclease in the induction of chromosomal DNA degradation in TCR-stimulated thymocytes."The Journal of Immunology. 165. 4281-4289 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimoda,K. et al: "Tyk2 plays a restricted role in IFN α signaling, although it is required for IL-12-mediated T cell function."Immunity. 13. 561-571 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto,T. et al: "Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling."FEBS Letters. 486. 143-148 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tong J-J., Kishi H., Nagata T., and Muraguchi A.: "Co-ordinate expression of pre-T-cell receptor complex and novel immature thymocyte-specific antigen during thymocyte development."Immnology. 96. 48-56 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasukawa H., Misawa H., Sakamoto H., Masuhara, M., Sasaki A., Wakioka T., Ohtsuka S., Imaizumi T., Matsuda T., Ihle J.N.and Yoshimura A.: "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop."The EMBO Journal. 18. 1309-1320 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tong J-J., Kishi H., Nagata T., and Muraguchi A.: "A bone marrow-derived stroma cell line, ST2, can support the differenriation of fetal thymocytes from the CD4-CD8- double negative to the CD4+CD8+ double positive differntiation stage in vitro."Immunology. 97. 672-678 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishi H., Wei X.-C., Jin Z.-X., Fujishiro Y., Nagata, T., Matsuda T., and Muraguchi A.: "Lineage-specific regulation of the murine RAG-2 promoter : GATA-3 in T cells and Pax-5 in B cells."Blood. 95. 3845-3852 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawakami T., Nagata T., Muraguchi A., and Nishimura T.: "Alteration of protein composition in mouse thymocytes by signals through T-cell receptor."Electrophoresis. 21. 1846-1852 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda T., Yamamoto T., Kishi H., Yoshimura A., and Muraguchi A.: "SOCS-1 can suppress CD3ζ-and Syk-mediated NF-AT activation in a non-lymphoid cell line."FEBS Letters. 472. 235-240 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata T., Kishi H., Liu Q.-L., Yoshino T., Matsuda T., Jin Z.-X., Murayama K., Tsukada K., and Muraguchi A.: "Possible involvement of cyclophilin B and caspase-activated deoxyri bonuclease in the inducition of chromosomal DNA degradation in TCR-stimulated thymocytes."J.Immunol.. 165. 4281-4289 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimoda K., Kato K., Aoki K., Matsuda T., Miyamoto A., Shibamori M., Yamashita M., Numata, A., Takase K., Kobayashi S., Shibata S., Asano Y., Gondo H., Sekiguchi K., Nakayama K., Nakayama T., Okamura T., Okamura S., Niho Y., and Nakayama K.: "Tyk2 plays a restricted role in IFN α signaling, although it is required for IL-12-mediated T cell function."Immunity. 13. 561-571 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto T., Matsuda T., Junicho A., Kishi H., Saatcioglu F., and Muraguchi A.: "Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling."FEBS Letters.. 486. 143-148 (2000)

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

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Published: 2002-03-26  

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