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Structural and genetic analysis of proteasomes

Research Project

Project/Area Number 08458182
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionThe Tokyo Metropolitan Institute of Medical Science

Principal Investigator

TANAKA Keiji  The Tokyo Metropolitan Institute of Medical Science, Researcher, 化学療法研究部門, 研究員 (10108871)

Co-Investigator(Kenkyū-buntansha) KAWAHARA Hiroyuki  The Tokyo Metropolitan Institute of Medical Science, Department of Radiation Res, 化学療法部, 研究員 (70291151)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥4,300,000 (Direct Cost: ¥4,300,000)
Keywordsproteasome / ubiquitin / gene disruption / structure-function relationship / proteolysis / cDNA cloning / primary structure / ATP-dependent protease / cDNAクローニング / 蛋白質分解 / 構造-機能相関 / 細胞周期 / タンパク質分解 / ATPase
Research Abstract

The 26S proteasome, a eukaryotic ATP-dependent protease, is a large multisubunit complex with a molecular weight of 2000 kDa, consisting of over 40 distinct components. It is a cumbbell-like particle, consisting of a cylindrical catalytic machine (termed the 20S proteasome) and two terminal modules (named PA700 or 19S complex), having possible regulatory functions, that is attached to both ends of the central portion in opposite orientations to form the enzymatically active proteasome. PA700 contains more than 20 heterogeneous subunits of 25-110 kDa, which can be classified into two subgroups : a subgroup of at least six ATPases that are structurally similar and highly conserved in evolution, and a subgroup of over 15 heterogeneous subunits that are structurally unrelated to the members of the ATPase family. During this research period, we have determined primary structures of ten new regulatory subunits containing two novel ATPase subunits of the human 26S proteasome by protein-chemical and molecular-biological techniques. By these results and together with our previous reports, we have succeeded to isolate cDNAs encoding most of all components of the 26S proteasome complec, providing structural information of this multisubunit complex at molecular level.Moreover we have carried out genetic analysis in Saccaromyces cerevisiae to clarify the cellular functions of individual subunit and found that proteasomes are essential for proliferation of the yeast cells. Intruguingly, some of non-ATPase subunits were indespensable for cell viability, unlike essential roles of most catalytic 20S proteasomal and 6 regulatory ATPase subunits, suggesting that they may have redundant functions. Structural and genetic results obtained by present study could provide important information to clarify the structure-function relationships of the 26S proteasome.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kominami, K.al.: "Ninlp,a regulatory subunit of the 26S proteasome is necessary for activation of Cdc28p kinase of Saccharomyces cerevisiae" EMBO.J.14. 3105-3115 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsurumi, C.et.al.: "Degradation of c-Fos by the 26S proteasome is acceralated by c-Jun and multiple protein kinases" Mol.Cell.Biol.15. 5682-5687 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokota, K.et.al.: "cDNA encoding of p112,a largest regulatory subunit of the human 26S proteasome and functional analysis of its yeast homologue.Sen3p" Mol,Biol.Cell. 7. 853-870 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Coyx, O.et.al.: "Structure and functions of the 20S and 26S proteasome" Annu.Rev.Biochem. 65. 801-847 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saito, A.et.al.: "cDNA cloning and functional analysis of p44.5 and p55,two regulatory subunits.of the 26S proteasome" Gene. 203. 241-250 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, K.: "Proteasomes:structure and biology" J.Biochem. 123. 195-204 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, K.: "Preparation of proteasomes.in"Cell Biology:A Laboratory Handbook"" Academic Pres,New York, 129-134 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawahara, H.andTank, K.: "Proteasomes:The protein death machinery in"Structure and Function of Molecular Chaperones:The Role of Chaperones in the Life Cvcle of Proteins"" Marcel Dekker(in press), (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kominami, K.et.al.: "Nimop, a regulatory subunit of the 26S proteasome is necessary for activation of Cdc28p kinase of Saccharomyces cerevisiae" EMBO J.14. 3105-3115 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsurumi, C.et.al.: "Degradation of c-Fos by the 26S proteasome is acceralated by c-Jun and multiple protein kinases" Mol.Cell.Biol.15. 5682-5687 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yokota, K,et.al.: "cDNA encoding of p112, a largest regulatory subunit of the humman 26S proteasome and functional analysis of its yeast homologue, Sen3p" Nol.Biol.Cell. 7. 853-870 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Coux, O.et.al.: "Structure and functions of the 20S and 26S proteasomes" Annu.Rev.Biochem. 65. 801-847 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Saito, A.et.al.: "cDNA cloning and functional analysis of p44.5 and p55, two regulatory subunits, of the 26S proteasome" Gene. 203. 241-250 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, K.: "Proteasomes : structure and biology" J.Biochem. 123. 195-204 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, K.: Academic Pres, New York. Preparation of proteasomes.in "Cell Biology : A Laboratory Handbook", 129-134 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawahara, H.and Tanaka, K.: Marcel Dekker in press. Proteasomes : The protein death machinery in "Structure and Function of Molecular Chaperones : The Role of Chaperones in the Life Cycle, (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kominami,K.et.al.: "Yeast counterparts of subunits S5a and P58(S3)of the human 26S proteasome are encoded by two multicopy supressors of nin1-1" Mol.Biol.Cell. 8. 171-187 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanahashi,N.et.al.: "Molecular properties of the proteasome activator PA28 family proteins and-interferon regulation" Genes to Cells. 2. 195-211 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Saito.A.et.al.: "cDNA cloning and functional analysis of p44.5 and p55,two regulatory subunits,of the 26S proteasome" Gene.

    • Related Report
      1997 Annual Research Report
  • [Publications] Shinbara,N.et.al.: "Double-cleavage production of the CTL epitope by proteasomes and PA28:role of the flanking region" Genes to Cells. 2. 785-800 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,K.: "Proteasomes and antigen processing" Adv.Immunol. 64. 1-38 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,K.: "Proteasomes:structure and biology" J.Biochem. 123. 195-204 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,K.: "Preparation of proteasomes,in "Cell Biology,A Laboratory Handbook"" Academic Press New York 2nd edition,part2., 129-134 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,K.: "Proteasomes: The protein death machirary In "Molecular Chaperones in the Life Cycle of Proteins:Structure Function,and Mode of Action"" Marcel Dekker,Inc.(in press), (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hisamotsu,H: "Newly identified pair of proteasomal subunits regulated reciprocally by interferon-γ" J.Exp.Med. 183. 1807-1816 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokota,K: "Molecular cloning of cDNA encoding a largest regulatory subunit p112 of the human 265 proteasome and functional analysis of its homolog sen3p in burlding yeas" Mol.Biol.Cell. 7. 853-870 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshida,H: "Accelerated degradation of PML-RARA oncoprotein by all-trans retinoic acid in acute preyeflocytic leukemia : Possible role of the proteasome pathway" Cancer Res. 56. 2945-2948 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Turumi,C: "cDNA clonig and functional anolysis of the p97 subunit of the 26s proteasome,a polypeptide identical to the type ITNF receptor binding protein TRAP-2155.11" Eur.J.Biochem. 239. 912-921 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kasahara,M: "Chromosonal localization of the proteasome Z subuinr gene reveals an ancient chromosonal duplication in volring the major histocom-patibility complex" Proc.Natl.Acad.Sci.USA.93. 9096-9101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Coux,O: "Saructure and functions of the 20s and 26s proteasomes" Annu.Rev.Biochem. 65. 801-847 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,K: "Preparation of proteasomes.in ″Cell Biology : A Laboratory Hand book″ 2nd edition" Academic Press,New York (in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawahara,H and Tanaka,K: "Proteasomes : The protein dcath machinery in ″Structure and Function of Molecular Chaperones & The Role of chaperones in the Life Cycle of Proteins″" Marcel Dekker (in press), (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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