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Quality control mechanism for positive and negative

Research Project

Project/Area Number 16207013
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKyoto University

Principal Investigator

NAGATA Kazuhiro  Kyoto University, Institute for Frontier Medical Sciences, Prof., 再生医科学研究所, 教授 (50127114)

Co-Investigator(Kenkyū-buntansha) HOSOKAWA Nobuko  Kyoto University, Institute for Frontier Medical Sciences, Assoc. Professor, 再生医科学研究所, 助教授 (00263153)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2006: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
KeywordsMolecular Chaperone / Quality control / ER associated degradation / EDEM
Research Abstract

We found and cloned the gene of a novel stress protein HSP47 which resides in the endoplasmic reticulum (ER) acting as a collagen-specific molecular chaperone in the pathway of collagen biosynthesis, processing and secretion. In addition to the binding specificity to collagen, the expression of HSP47 is always closely correlated with those of collagens during the normal development of mouse embryo as well as in the pathophysiological conditions including liver and renal fibrosis.
We are also working on the intracellular mechanism of ERQC (ER quality control) including ERAD (ER associated degradation). We have cloned a mouse gene EDEM, and EDEM family proteins, which are involved in the ERAD of glycoproteins. Furthermore, we also identified and cloned ERdj5 as EDEM-binding J-domain-containing chaperone-like protein in the ER, which we showed is involved in ERAD as a novel reductase in the ER.
We are also studying cytosolic chaperonin CCT and showed that CCT prevents the aggregation of poly-glutamine containing proteins. This finding is directly related to the development of therapeutic strategy for neurodegenerative diseases.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (37 results)

All 2007 2006 2005 2004 Other

All Journal Article (35 results) Book (2 results)

  • [Journal Article] Simultaneous induction of the four subunits of TRAP complex by ER stress accelerates ER degradation.2007

    • Author(s)
      K.NAgasawa
    • Journal Title

      EMBO reports 8(5)

      Pages: 483-490

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Simultaneous induction of the four subunits of TRAP complex by ER stress accelerates ER degradation.2007

    • Author(s)
      K.Nagasawa
    • Journal Title

      EMBO reports 8(5)

      Pages: 483-490

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Specific recognition of the collagen triple helix by chaperone HSP47. Minimal structural requirement and spatial molecular orientation.2006

    • Author(s)
      T.Koide
    • Journal Title

      J. Biol. Chem. 281(6)

      Pages: 3432-3438

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.2006

    • Author(s)
      Y.Oda
    • Journal Title

      J. Cell. Biol. 172(3)

      Pages: 383-393

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EDEM3, a soluble EDEM homolog, enhances glycoprotein ERAD and mannose trimming.2006

    • Author(s)
      K.Hirao
    • Journal Title

      J. Biol. Chem. 281(14)

      Pages: 9650-9658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded α 1-antitrypsin.2006

    • Author(s)
      N.Hosokawa
    • Journal Title

      Genes Cells. 11(15)

      Pages: 465-476

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Type I collagen in Hsp47-null cells is aggregated in ER and deficient in N-propeptide processing and fibrillogenesis2006

    • Author(s)
      Y.Ishida
    • Journal Title

      Mol. Biol. Cell. 17

      Pages: 2346-2355

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands2006

    • Author(s)
      S.Kubota
    • Journal Title

      Proc. Natl. Acad. Sci. USA 103(22)

      Pages: 8360-9365

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state.2006

    • Author(s)
      A.Kitamura
    • Journal Title

      Nature Cell Biol. 8(10)

      Pages: 1163-1169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded a 1-antitrypsin.2006

    • Author(s)
      N.Hosokawa
    • Journal Title

      Genes Cells. 11(15)

      Pages: 465-476

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state.2006

    • Author(s)
      A.KITAMURA et al.
    • Journal Title

      Nature Cell Biol. 8.1

      Pages: 1163-1169

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands2006

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

      Proc. Natl. Acad. Sci. USA 103.22

      Pages: 8360-8365

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Type I collagen in Hsp47-null cells is aggregated in ER and deficient in N-propeptide processing and fibrillogenesis2006

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

      Mol. Biol. Cell. 17

      Pages: 2346-2355

    • Related Report
      2006 Annual Research Report
  • [Journal Article] EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded α 1-antitrypsin.2006

    • Author(s)
      N.HOSOKAWA et al.
    • Journal Title

      Genes Cells. 11.15

      Pages: 465-476

    • Related Report
      2006 Annual Research Report
  • [Journal Article] EDEM3, a soluble EDEM homolog, enhances glycoprotein ERAD and mannose trimming.2006

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

      J. Biol. Chem. 281.14

      Pages: 9650-9658

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.2006

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

      J. Cell. Biol. 172.3

      Pages: 383-393

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage.2006

    • Author(s)
      M.NAITOH et al.
    • Journal Title

      Genes Cells. 10・11

      Pages: 1081-1091

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.2006

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

      J.Cell.Biol. 172・3

      Pages: 383-393

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The maintenance of the endoplasmic reticulum network is regulated by p47, a cofactor of p97, through phosphorylation by cdc2 kinase.2005

    • Author(s)
      F.Kano
    • Journal Title

      Genes Cells. 10(4)

      Pages: 333-344

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage.2005

    • Author(s)
      M.Naitoh
    • Journal Title

      Genes Cells. 10(11)

      Pages: 1081-1091

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] NSF/SNAPs and p97/p47/VCIP135 are sequentially required for cell cycle-dependent reformation of the ER network.2005

    • Author(s)
      F.Kano
    • Journal Title

      Genes Cells. 10(10)

      Pages: 989-999

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The maintenance of the endoplasmic reticulum network is regulated by p4'7, a cofactor of p97, through phosphorylation by cdc2 kinase.2005

    • Author(s)
      F.Kano
    • Journal Title

      Genes Cells. 10(4)

      Pages: 333-344

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Insufficient folding of type IV collagen nad formation of abnormal basement membrane-like structure in embryoid bodies derived from HSP47-null ES cells.2004

    • Author(s)
      Y.Matsuoka
    • Journal Title

      Mol. Biol. Cell. 15

      Pages: 4467-4475

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Accumulation of type IV collagen in dilated endoplasmic reticulum leads to apoptosis HSP47-knockout mouse embryos through the induction of CHOP.2004

    • Author(s)
      T.Marutani
    • Journal Title

      J.Cell.Sci. 117

      Pages: 5913-5922

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Accumulation of type IV collagen in dilated endoplasmic reticulum leads to apoptosis HSP47-knockout mouse embryos through the induction of CHOP.2004

    • Author(s)
      T.Marutani
    • Journal Title

      J. Cell. Sci. 117

      Pages: 5913-5922

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The endoplasmic reticulum stress response is stimulated through the continuous activation of transcrption factors ATF6 and XBP1 in Ins2^<+/Akita> pancreatic b ceils.2004

    • Author(s)
      J.NOZAKI et al.
    • Journal Title

      Genes Cells 9

      Pages: 261-270

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy.2004

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

      J. Biol. Chem. 279

      Pages: 19816-19823

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of multiple members of the HSP7O family in platyfish culture cells : molecular evolution of stress protein HSP7O in vertebrates.2004

    • Author(s)
      M.YAMASHITA et al.
    • Journal Title

      Gene 336

      Pages: 207-218

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Insufficient folding of type IV collagen nad formation of abnormal basement membrane-like structure in embryold bodies derived from HSP47-null ES cells.2004

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

      Mol. Biol. Cell. 15

      Pages: 4467-4475

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Accumulation of type IV collagen in dilated endoplasmic reticulum leads to apoptosis HSP47-knockout mouse embryos through the induction of CHOP.2004

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

      J. Cell. Sci. 117

      Pages: 5913-5922

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum.2004

    • Author(s)
      S.J.MARCINIAK et al.
    • Journal Title

      Genes Develop. 18

      Pages: 3066-3077

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Specific recognition of the collagen triple helix by chaperone HSP47. Minimal structural requirement and spatial molecular orientation.

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

      J.Biol.Chem. in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] EDEM3, a soluble EDEM homolog, enhances glycoprotein ERAD and mannose trimming.

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

      J.Biol.Chem. in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] EDEM accelerates ERAD by preventing aberrant dimer formation of misfolded α1-antitrypsin has been accepted for publication.

    • Author(s)
      N.HOSOKAWA et al.
    • Journal Title

      Genes Cells. in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Type I collagen in Hsp47-null cells is aggregated in ER and deficient in N-propeptide processing and fibrillogenesis

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

      Mol.Biol.Cell. in press

    • Related Report
      2005 Annual Research Report
  • [Book] Topics in Current Chemistry : Collagen 2472005

    • Author(s)
      T.KOIDE, K.NAGATA
    • Publisher
      Springer-Verlag
    • Related Report
      2005 Annual Research Report
  • [Book] Topics in Current Chemistry : Collagen(EdsBrinckmann et al.)(Collagen Biosynthesis)2005

    • Author(s)
      T.KOIDE et al.
    • Publisher
      Springer- Verlag(in press)
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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