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2005 Fiscal Year Final Research Report Summary

The oxytocinase subfamily of M1 aminopeptidases

Research Project

Project/Area Number 15390032
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionRIKEN

Principal Investigator

TSUJIMOTO Masafumi  RIKEN, Lab.of Cell.Biochem., Chief Scientist, 辻本細胞生化学研究室, 主任研究員 (00281668)

Co-Investigator(Kenkyū-buntansha) HATTORI Akira  RIKEN, Lab.of Cell.Biochem., Senior Research Scientist, 辻本細胞生化学研究室, 先任研究員 (50300893)
MASUDA Shinako  RIKEN, Lab.of Cell.Biochem., Special Postdoctral Researcher, 辻本細胞生化学研究室, 基礎科学特別研究員 (30342851)
TANIOKA Toshihiro  RIKEN, Lab.of Cell.Biochem., Special Postdoctral Researcher, 辻本細胞生化学研究室, 基礎科学特別研究員 (80360585)
Project Period (FY) 2003 – 2005
KeywordsAminopeptidase / Oxytocinase Subfamily / Placental Leucine Aminopeptidase / Adipocyte-derived Leucine Aminopeptidase / Leukocyte-derived Arginine Aminopeptidase / NRK52E Cells / MHC Class I Antigenic Peptides / ER Retention Mechanism
Research Abstract

In our previous works, we identified and cloned two aminopeptidases (P-LAP and A-LAP) as novel enzymes belonging to the M1 family of aminopeptidases. In addition, we showed that A-LAP is a final processing enzyme of peptide antigens presented to MHC class I molecules in the endoplasmic reticulum (ER). Based on these results, we further examined the structural and functional analyses of M1 family members in this study and we identified one novel aminopeptidase. In addition, we have performed the functional analyses of these three enzymes that we have identified.
By searching a database, we have identified and cloned a novel protein designated as leukocyte-derived arginine aminopeptidase (L-RAP). Since L-RAP is homologous to P-LAP and A-LAP, we are now proposing that these three enzymes should be classified into "The oxytocinase subfamily of M1 aminopeptidases".
Functional analyses of P-LAP indicated that after treatment of renal-derived NRK52E cells with vasopressin, rapid translocation of P-LAP from intracellular vesicles to plasma membranes was observed. Since vasopressin is a good substrate of the enzyme, these results suggest the existence of the P-LAP-mediated negative feedback mechanism of vasopressin action in the kidney.
As for A-LAP, we have analyzed its ER-retention mechanism and found a protein binding to the enzyme. Since this protein contains an ER-retention signal (HDEL) in its C-terminal end, it is plausible that A-LAP is retained in the ER via binding to the protein. Based on this result, we will further examine the total aspect of the ER-retention mechanism of the enzyme.
It was also found that L-RAP is localized in the luminal side of the ER and can process N-extended precursor peptide antigens presented to the MHC class I molecules to mature forms. These results indicate for the first time that L-RAP is the second ER-aminopeptidase that can trim N-extended precursors to antigenic peptides.

  • Research Products

    (22 results)

All 2006 2005 2004 2003

All Journal Article (22 results)

  • [Journal Article] Endoplasmic reticulum aminopeptidase 1 mediates leukemia inhibitory factor-induced cell surface HLA-G expression in JEG-3 choriocarcinoma cells2006

    • Author(s)
      Shido F. et al.
    • Journal Title

      Endocrinology 147

      Pages: 1780-1788

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-12006

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

      FEBS Letters 580

      Pages: 1833-1383

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] M1アミノペプチダーゼファミリーの新たな生理機能2006

    • Author(s)
      服部 明, 辻本雅文
    • Journal Title

      日本血栓止血学会誌 17

      Pages: 20-28

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Physiological roles of M1 aminopeptidase family2006

    • Author(s)
      Hattori A., Tsujimoto M.
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis 17

      Pages: 20-28

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of the human leukocyte-derived arginine aminopeptidase/ER-aminopeptidase 2 gene by interferon-γ2005

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

      FEBS Journal 272

      Pages: 916-928

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The oxytocinase subfamily of M1 aminopeptidases2005

    • Author(s)
      Tsujimoto M., Hattori A.
    • Journal Title

      Biochimica et Biophysica Acta 1751

      Pages: 9-18

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 小胞体アミノペプチダーゼの発見とMHCクラス-I抗原ペプチドプロセシングにおける役割2005

    • Author(s)
      服部 明, 辻本雅文
    • Journal Title

      化学と生物 43

      Pages: 739-745

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Endoplasmic reticulum aminopeptidases2005

    • Author(s)
      Hattori A., Tsujimoto M.
    • Journal Title

      Kagaku To Seibutsu 43

      Pages: 739-745

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase2004

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

      Biochemical and Biophysical Research Communications 314

      Pages: 1008-1013

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Distribution of Adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase(ERAP)-1 in human uterine endometrium2004

    • Author(s)
      Shibata D. et al.
    • Journal Title

      Journal of Histochemistry and Cytochemistry 52

      Pages: 1169-1175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Processing of antigenic peptidases by aminopeptidases2004

    • Author(s)
      Hattori A., Tsujimoto M.
    • Journal Title

      Biological and Pharmaceutical Bulletin 27

      Pages: 777-780

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Distribution of Adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in human uterine endometrium2004

    • Author(s)
      Shibata D. et al.
    • Journal Title

      Journal of Histochemistry and Cytochemistry 52

      Pages: 1169-1175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Processing of antigenic peptidases by aminopeptidases2004

    • Author(s)
      Hattori A., Tsujimoto M.
    • Journal Title

      Biological and Pharmaceutical.Bulletin 27

      Pages: 777-780

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of the V2 receptor in vasopressin-stimulated translocation of placental leucine aminopeptidase/oxytocinase in renal cells2003

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

      European Journal of Biochemistry 270

      Pages: 1988-1994

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human leukocyte-derived arginine aminopeptidase : the third member of the oxytocinase subfamily of aminopeptidase2003

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

      Journal of Biological Chemistry 278

      Pages: 32275-32283

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] オキシトシナーゼサブファミリー-M1アミノペプチダーゼの新しいサブファミリーの同定とその生理機能2003

    • Author(s)
      服部 明, 辻本雅文
    • Journal Title

      生化学 75

      Pages: 1225-1230

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of adipocyte-derived leucine aminopeptidase in endometrial cancer : Association with tumor grade and CA-1252003

    • Author(s)
      Kasato H. et al.
    • Journal Title

      Tumor Biology 24

      Pages: 203-208

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible role of placental leucine aminopeptidase in the antiproliferative effect of oxytocin in human endometrial adenocarcinoma2003

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

      Clinical Cancer Research 9

      Pages: 1528-1534

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein-2 in BeWo cell model of human trophoblast differentiation2003

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

      FEBS Letters 552

      Pages: 120-124

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Adipocyte-derived leucine aminopeptidase (A-LAP) suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system (RAS)2003

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

      Clinical Cancer Research 9

      Pages: 6497-6503

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells2003

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

      Laboratory Investigation 83

      Pages: 1799-1810

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The oxytocinase subfamily of M1 aminopeptidases2003

    • Author(s)
      Hattori A., Tsujimoto M
    • Journal Title

      SEIKAGAKU 70

      Pages: 1225-1230

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

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Published: 2007-12-13  

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