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RESEARCH FOR THE MHC CLASS I RESTRICTED ANTIGEN PROCESSING AND PRESENTATION

Research Project

Project/Area Number 06671592
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionTHE UNIVERSITY OF TOKUSHIMA

Principal Investigator

AKIYAMA Kinya (1995)  UNIVERSITY HOSPITAL OF SCHOOL OF MEDICINE,THE UNIVERSITY OF TOKUSHIMA,ASSISTANT, 医学部・附属病院, 助手 (30263833)

安芸 雅史 (1994)  徳島大学, 医学部・附属病院, 助手 (40231815)

Co-Investigator(Kenkyū-buntansha) YOKOTA Kinya  UNIVERSITY HOSPITAL OF SCHOOL OF MEDICINE,THE UNIVERSITY OF TOKUSHIMA,ASSISTANT, 医学部・附属病院, 助手 (10274218)
TANAKA Keiji  INSTITUTE FOR ENZYME RESEARCH,THE UNIVERSITY OF TOKUSHIMA,ASSOCIATE PROFESSOR, 酵素科学研究センター, 助教授 (10108871)
秋山 欣也  徳島大学, 医学部・附属病院, 助手 (30263833)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsPROTEASOME / ANTIGEN PROSECCING / ANTIGEN PRESENTATION / INTERFERON-gamma / ACTIVATING FACTOR / γ型インターフェロン / プロテアソーム活性化因子 / MHCクラスI
Research Abstract

The proteasome is a unusually large multifunctional protease complex consisting of multiple polypeptides, which catalyzes non-lysosomal, ATP-dependent selective breakdown of ubiquitinated proteins and is thought to be a putative processing enzyme responsible for major histocompatibility complex (MHC) class I-restricted antigen presentation. Recently, we reported that a major immunomodulatory cytokine, gamma interferon (gamma-IFN), induced not only marked synthesis of the MHC-encoded proteasome subunits LMP2 and LMP7, but also almost complete loss of two unidentified proteasome subunits tentatively designated as X and Y in various human cells, which alters the proteolytic specificity of proteasomes perhaps more appropriate for the immunological processing of endogenous antigens. Based on partial amino acid sequence analysis of X and Y,we suggested that subunit X is a proteasomal subunit similar to LMP7, and that subunit Y is identical to the LMP2-related proteasomal subunit delta. Final … More ly, molecular cloning of cDNAs encoding X and Y showed that these X and Y are a novel class of proteasomal subunits with high homology to LMP7 and LMP2, respectively. Moreover, recently we found two novel proteasome subunits expressed reciprocally in response to interferon-gamma. Molecular cloning of a cDNA encoding one subunit designated as Z down-regulated by interferon-gamma showed that it is a novel proteasomal subunit with high homology to MECL1, which is markedly induced by interferon-gamma (Submitted for publication). Thus, interferon-gamma may induce subunit replacements of not only X and Y by LMP7 and LMP2, respectively, but also of Z by MECL1, producing proteasomes responsible for major histocompatibility complex (MHC) class I-restricted antigen presentation.
The primary structures of two proteins that comprise PA28, an activator of the 20S proteasome, have been determined by cDNA cloning and sequencing. These protein subunits, termed PA28a and PA28b, are about 50% identical to one another and are highly conserved between rat and human. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Masashi Aki: "Interferon-γ Induces Different Subunit Organizations and Functional Diversity of Proteasomes" Journal of biochemistry. 115. 257-269 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kinya Akiyama: "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by interferon-γ for acquirement of the functional diversity responsible for antigen processing" FEBS Letters. 343. 85-88 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kinya Akiyama: "cDNA Cloning and Interferon γ Down-Regulation of Proteasomal Subunits X and Y" Science. 265. 1231-1234 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 田中啓二: "内在性抗原のプロセシングとその提示" 実験医学. 12. 71-77 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 田中啓二: "抗原プロセシングのメカニズム" Molecular Medicine. 32. 6-11 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Joon Young Ahn: "Primary structures of two homologous subunits of PA28,aγ-interferon-inducible protein activator of the 20S proteasome" FEBS Letters. 366. 37-42 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masashi Aki, Kinya Akiyam, Keiji Tanaka, Susumu Kagawa et al: "Interferon-gamma Induces Different Subunit Organizations and Functional Diversity of Proteasomes" J.Biochem. 115. 257-269 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kinya Akiyama, Keiji Tanaka, Susumu Kagawa et al: "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by interferon-gamma for acquirement of the functional diversity responsible for antigen processing" FEBS Letters. 343. 85-88 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kinya Akiyama, Kinya Yokota, Keiji Tanaka, Susumu Kagawa et al: "cDNA Cloning and Interferon gamma Down-Regulation of Proteasomal Subunits X and Y" Science. 265. 1231-1234 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Keiji Tanaka, Kin-ya Akiyama, Hiroshi Hisamatsu: "Processing and presentation of endogenous antigens" Experimental Medicine. 12. 71-77 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Keiji Tanaka, Kin-ya Yokota: "Mechanism of antigen processing" Molecular Medicine. 32. 6-11 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Joon Young Ahn, Kinya Akiyama, Teiji Tanaka et al: "Primary structures of two homologous subunits of PA28, a gamma-interferon-inducible protein activator of the 20S proteasome" FEBS Letters. 366. 37-42 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 秋山欣也: "primary structures of two homologous subunits of PA28, a γ-interferon-inducible protein activator og the 20S proteasome" FEBS letters. 366. 37-42 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 久松浩: "Newly identified pair of proteasomal subunits regulated reciprocally by interferon-γ" Journal of experimental medicine. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 秋山欣也: "cDNA Cloning and Interferon _γ Down-Regulation of Proteasomal Subunits X and Y" Science. 265. 1231-1234 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 安芸雅史: "Interferon-_γ Induces different Subunit Organizations and Functional Diversity of Proteasomes" The Journal of Biochemistry. 115. 257-269 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 秋山欣也: "Replacement of Proteasome Subunits X and Y by LMP7 and LMP2 Induced by Interferon-_γ for Acquirement of the Functional Diversity Responsible for Antigen Processing" FEBS Letters. 343. 85-88 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田中啓二: "内在性抗原のプロセッシングとその提示" 免疫研究の最前線(実験医学増刊). 12. 71-77 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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