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Analysis of the biosynthetic mechanism and functions of glycosaminogycans by manipulating the genes encoding biosynthetic enzymes.

Research Project

Project/Area Number 13470493
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKobe Pharmaceutical University

Principal Investigator

SUGAHARA Kazuyuki  Kobe Pharmaceutical University, Dept.of Biochemistry, Professor, 薬学部, 教授 (60154449)

Co-Investigator(Kenkyū-buntansha) KITAGAWA Hiroshi  Kobe Pharmaceutical University, Dept.of Biochemistry, Assistant Professor, 薬学部, 助教授 (40221915)
YAMADA Shuhei  Kobe Pharmaceutical University, Dept.of Biochemistry, Lecuture, 薬学部, 講師 (70240017)
MIKAMI Tadahisa  Kobe Pharmaceutical University, Dept.of Biochemistry, Instructor, 薬学部, 助手 (20330425)
ASANO Masahide  Kanazawa University, Advanced Science Research Center, Professor, 学際科学実験センター, 教授 (50251450)
TAYA Choji  The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Dept.of Laboratory Animal Science, Chief Scientist, 東京都臨床医学総合研究所・実験動物部門, 主任研究員 (90175456)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywordsglycosaminoglycan / heparan sulfate / chondroitin sulfate / glycosyltransferase / sulfotransferase / chondroitin synthase / chondroitin polymerizing factor / RNAi / ガン抑制遺伝子 / EXT / プロテオグリカン / 線虫 / 糖転位酵素 / グルクロン酸転位酵素 / ショウジョウバエ / シンデカン / グルクロン酸転移酵素 / N-アセチルガラクトサミン転移酵素
Research Abstract

(1) Human EXTL1 and EXTL3 were demonstrated for the first time to exhibit glycosyltransferase activities involved in heparan sulfate synthesis.
(2) Human chondrotiin synthase was cloned for the first time.
(3) It was demonstrated that acceptor core protein moieties in addition to an enzyme complex of human EXT1 and EXT2 for heparan sulfate polymerization.
(4) Human chondroitin polymerizing factor required for chain polymerization of chondroitin was cloned for the first time.
(5) Chondroitin/dermatan 4-O-sulfotransferases were cloned and their detailed substrate specificity was characterized.
(6) It was found that one of the Gal residues in the GAG-protein linkage region tetrasaccharide is sulfated in the chondroitin sulfate chains but not in the heparan sulfate chains of a hybrid type proteoglycan syndecan-1.
(7) The crystal structure of EXTL2, which exhibits GlcNAc transferase activity, was demonstrated for the first time.
(8) Choncdoirin was demonstrated to be essential for the embryonic cell division of C.elegans.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All 2003 2002 2001 Other

All Journal Article (24 results) Publications (13 results)

  • [Journal Article] Crystal structure of an α1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis.2003

    • Author(s)
      Pedersen, L.C.
    • Journal Title

      J.Biol.Chem. 278(16)

      Pages: 14420-14428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Chondroitin proteoglycans are involved in cell division of Caenorhabsitis elegans2003

    • Author(s)
      水口 惣平
    • Journal Title

      Nature 423(6938)

      Pages: 443-448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning of a chondoroitin polymerizing factor that cooperates with chondroitin synthase for chondoroitin polymerization.2003

    • Author(s)
      北川 裕之
    • Journal Title

      J.Biol.Chem. 278(26)

      Pages: 23666-23671

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor : Implication of differential roles in dermatan sulfate biosynthesis.2003

    • Author(s)
      三上 雅久
    • Journal Title

      J.Biol.Chem. 278(38)

      Pages: 36115-36127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] In Vitro Heparan Sulfate Polymerization : CRUCIAL ROLES OF CORE PROTEIN MOIETIES OF PRIMER SUBSTRATES IN ADDITION TO THE EXT1-EXT2 INTERACTION2003

    • Author(s)
      金 炳澤
    • Journal Title

      J.Biol.Chem. 278(43)

      Pages: 41618-41623

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Crystal structure of an α1, 4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis.2003

    • Author(s)
      Pedersen, Lars C.
    • Journal Title

      J.Biol.Chem. 278(16)

      Pages: 14420-14428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans.2003

    • Author(s)
      Mizuguchi, Souhei
    • Journal Title

      Nature 423(6938)

      Pages: 443-448

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization.2003

    • Author(s)
      Kitagawa, Hiroshi
    • Journal Title

      J.Biol.Chem. 278(26)

      Pages: 23666-23671

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor : Implication of differential roles in dermatan sulfate biosynthesis.2003

    • Author(s)
      Mikami, Tadahisa
    • Journal Title

      J.Biol.Chem. 278(38)

      Pages: 36115-36127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] In Vitro Heparan Sulfate Polymerization : CRUCIAL ROLES OF CORE PROTEIN MOIETIES OF PRIMER SUBSTRATES IN ADDITION TO THE EXT1-EXT2 INTERACTION.2003

    • Author(s)
      Kim, Byung-Taek
    • Journal Title

      J.Biol.Chem. 278(43)

      Pages: 41618-41623

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase : The key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate.2002

    • Author(s)
      宇山 徹
    • Journal Title

      J.Biol.Chem. 277(11)

      Pages: 8841-8846

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Determination of the glycosaminoglycan-protein linkage region oligosaccharide structure of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans.2002

    • Author(s)
      山田 修平
    • Journal Title

      J.Biol.Chem. 277(35)

      Pages: 31877-31886

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Heparin and heparan sulfate biosynthesis (comprehensive review).2002

    • Author(s)
      菅原 一幸
    • Journal Title

      IUBMB Life 54(4)

      Pages: 163-175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase. The key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate.2002

    • Author(s)
      Uyama, Toru
    • Journal Title

      J.Biol.Chem. 277(11)

      Pages: 8841-8846

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Determination of the glycosaminoglycan-protein linkage region oligosaccharide structures of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans.2002

    • Author(s)
      Yamada, Shuhei
    • Journal Title

      J.Biol.Chem. 277(35)

      Pages: 31877-31886

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Heparin and heparan sulfate biosynthesis (comprehensive review).2002

    • Author(s)
      Sugahara, Kazuyuki
    • Journal Title

      IUBMB Life 54(4)

      Pages: 163-175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Structural characterization of heparan sulfate and chondroitin sulfate of syndecan-1 purified from normal murine mammary gland epithelial cells. Common phosphorylation of xylose and differential sulfation of galactose in the protein linkage region tetradsaccharide sequence.2001

    • Author(s)
      上野 百世
    • Journal Title

      J.Biol.Chem. 276(31)

      Pages: 29134-29140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Human tumor suppressor EXT gene family members, EXTL1 and EXTL3 encode α1,4-N-acetylglucosaminyltransferase that likely are involved in heparan sulfate/heparin biosynthesis.2001

    • Author(s)
      金 炳澤
    • Journal Title

      Proc.Natl.Acad.Sci.USA 98(13)

      Pages: 7176-7181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Human glucosaminoglucan gluconyltransferase 1 gene and a related processed pseudogene : genomic structure, chromosomal mapping, and characterization.2001

    • Author(s)
      北川 裕之
    • Journal Title

      Biochem.J. 358(3)

      Pages: 539-546

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning and expression of a human chondroitin synthase.2001

    • Author(s)
      北川 裕之
    • Journal Title

      J.Biol.Chem. 276(42)

      Pages: 38721-38726

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Structural characterization of heparan sulfate and chondroitin sulfate of syndecan-1 purified from normal murine mammary gland epithelial cells. Common phosphorylation of xylose and differential sulfation of galactose in the protein linkage region tetrasaccharide sequence.2001

    • Author(s)
      Ueno, Momoyo
    • Journal Title

      J.Biol.Chem. 276(31)

      Pages: 29134-29140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Human tumor suppressor EXT gene family nembers, EXTL1 and EXTL3 encode α1, 4-N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/heparin biosynthesis.2001

    • Author(s)
      Kim, Byung-Taek
    • Journal Title

      Proc.Natl.Acad.Sd.USA 98(13)

      Pages: 7176-7181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Human glycosaminoglycan glucuronyltransferase I gene and a related processed pseudogene : genomic structure, chromosomal mapping, and characterization.2001

    • Author(s)
      Kitagawa, Hiroshi
    • Journal Title

      Biochem.J. 358(3)

      Pages: 539-546

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular cloning and expression of a human chondroitin synthase.

    • Author(s)
      Kitagawa, Hiroshi
    • Journal Title

      J.Biol.Chem. 276(42)

      Pages: 38721-38726

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lars C.Pedersen: "Crystal structure of an α1,4-N-acetylhexosaminyltransferase (EXTL2),a member of the exostosin gene family involved in heparan sulfate biosynthesis."J.Biol.Chem.. 278(16). 14420-14428 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 水口 惣平: "Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans."Nature. 423(6938). 443-448 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 北川 裕之: "Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization."J.Biol.Chem.. 278(26). 23666-23671 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 三上 雅之: "Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-Ο-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor : Implication of differential roles in dermatan sulfate biosynthesis."J.Biol.Chem.. 278(38). 36115-36127 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 金 炳澤: "In Vitro Heparan Sulfate Polymerization : CRUCIAL ROLES OF CORE PROTEIN MOIETIES OF PRIMER SUBSTRATES IN ADDITION TO THE EXT1-EXT2 INTERACTION"J.Biol.Chem.. 278(43). 41618-41623 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山田 修平: "Determination of the glycosaminoglycan-protein linkage region oligosaccharide structures of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans"J. Biol. Chem.. 277(35). 31877-31886 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菅原 一幸: "Heparin and heparan sulfate biosynthesis (comprehensive review)"IUBMB Life. 54(4). 163-175 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pedersen, L.C.: "Crystal structure of an α1, 4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis"J. Biol. Chem.. (印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] 上野 百世: "Structural Characterization of Heparan Sulfate and Chondroitin Sulfate of Syndecan-1 Purified from Normal Murine Mammary Gland Epithelial Cells. Common Phosphorylation of Xylose and Differential Sulfation of Galactose in the Protein Linkage Region Tetrasaccharide Sequence"J. Biol. Chem.. 276(31). 29134-29140 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 金 炳澤: "Human Tumor Suppressor EXT Gene Family Members, EXTL1 and EXTL3 Encode α1,4-N-Acetylglucosaminyltransferases That Likely Are Involved in Heparan Sulfate/Heparin Biosynthesis"Proc. Natl. Acad. Sci. USA. 98(13). 7176-7181 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北川 裕之: "Human Glycosaminoglycan Glucuronyltransferase I Gene and a Related Processed Pseudogene : Genomic Structure, Chromosomal Mapping, and Characterization"Biochem. J.. 358(3). 539-546 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北川 裕之: "Molecular Cloning and Expression of a Human Chondroitin Synthase"J. Biol. Chem.. 276(42). 38721-38726 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 宇山 徹: "Molecular Cloning and Expression of Human Chondroitin N-Acetylgalactosaminyltransferase : The Key Enzyme for Chain Initiation and Elongation of Chondroitin/Dermatan Sulfate on the Protein Linkage Region Tetrasaccharide Shared by Heparin/Heparan Sulfate"J. Biol. Chem.. 277(11). 8841-8846 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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