• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of protein L-isoaspartyl(D-aspartyl)methyltransferase in cellular functions

Research Project

Project/Area Number 18590070
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FURUCHI Takemitsu  Kitasato University, School of Phamaceutical Sciences, Lecturer (00302167)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsAspartate / Asparagine / PIMT / Isomerization / Racemization / protein repair enzyme
Research Abstract

Proteins are subject to various types of spontaneous modifications that can disrupt their structures with sometimes adverse affects on biological activity. The formation of L-isoaspartyl (or D-aspartyl) residues, through either the deamidation of asparagine or dehydration of aspartate, is one of the most frequent types of deterioration occurring under physiological conditions. Protein L-isoaspartate/D-aspartate o-methyltransferase (PIMT) is a conserved and ubiquitous enzyme that participates in the repair of various isomerized proteins. PIMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine onto the α-carboxyl group of an L-isoaspartyl (or the b-carboxyl group of an D-aspartyl) residue, which initiates the conversion of this residue to an L-aspartyl residue. PIMT-deficient mice have been shown to die at a mean age of 42 days from progressive epileptic seizures with grand mal and myoclonus. Although PIMT-deficiency clearly leads to the accumulation of isomerized proteins, it is currently unclear how this causes progressive epilepsy in PIMT-deficient mice. As a first step towards understanding this, we developed a new assay to measure PIMT activity in cell lysates. We also analyzed PIMT promoter activity using Luciferase Reporter Gene Assay System and identified an element essential for transcriptional activation. Additionally, we isolated PIMT knockdown cells from HEK293 cells that were stably transfected with a PIMT small interfering RNA expression vector. PIMT activities were significantly decreased in the PIMT knockdown cells, and analysis of the transfectants revealed that MEK and ERK were hyperactivated after cell stimulation with epidermal growth factor (EGF). These results indicate that the ability to repair L-isoaspartyl-(or D-aspartyl-)containing proteins is important for the maintenance of normal MEK-ERK signaling.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (41 results)

All 2008 2007 2006 2005 Other

All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (14 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Hyperactive mutants of mouse D-aspartate oxidase: mutagenesis of the active site residue serine 3082008

    • Author(s)
      Katane, Masumi
    • Journal Title

      Amino Acids 31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cloning and functional characterization of Arabidopsis thaliana D-amino acid ami notransferase-D-aspartate behavior during germination2008

    • Author(s)
      Funakoxhi, Miya
    • Journal Title

      FEBS J. 275

      Pages: 1188-1200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Suppression of protein l-isoaspartyl (d-aspartyl) methyltransferase results in hyperactivation of EGF-stimulated MEK-ERK signaling in cultured mammalian cells2008

    • Author(s)
      Kosugi, Sakurako
    • Journal Title

      Biochem.Biophys.Res.Commun 371

      Pages: 22-27

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The ubiquitin-conjugating enzymes,Ubc4 and Cdc34,mediate cadmium resistance in budding yeast through different mechanisms2008

    • Author(s)
      Gi-Wook, Hwang
    • Journal Title

      Life Sci 82

      Pages: 1182-1185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hyperactive mutants of mouse D : -aspartate oxidase : mutagenesis of the active site residue serine 3082008

    • Author(s)
      Katane, M., Hanai, T., Furuchi, T., Sekine, M., Homma, H
    • Journal Title

      Amino Acids (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cloning and functional characterization of Arabidopsis thaliana D-amino acid aminotransferase-D-aspartate behavior during germination2008

    • Author(s)
      Funakoshi, M., Sekine, M., Katane, M., Furuchi, T., Yohda, M., Yoshikawa, T., Homma, H
    • Journal Title

      FEBS J 275(6)

      Pages: 1188-1200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Suppression of protein l-isoaspartyl(d-aspartyl)methyltransferase results in hyperactivation of EGF-stimulated MEK-ERK signaling in cultured mammalian cells2008

    • Author(s)
      Kosugi, S., Furuchi, T., Katane, M., Sekine, M., Shirasawa, T., Homma, H
    • Journal Title

      Biochem Biophys Res Commun 371(1)

      Pages: 22-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The ubiquitin-conjugating enzymes, Ubc4 and Cdc34, mediate cadmium resistance in budding yeast through different mechanisms2008

    • Author(s)
      Hwang, GW., Furuchi, T., Naganuma, A
    • Journal Title

      Life Sci 82(23-24)

      Pages: 1182-1185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hyperactive mutants of mouse D-aspartate oxidase:mutagenesis of the active site reridue serine 308.2008

    • Author(s)
      Katane, Masumi
    • Journal Title

      Amino Acids 31(In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caenorhabditis elegans has two genes encoding functional D-aspartate oxi dases2007

    • Author(s)
      Katane, Masumi
    • Journal Title

      FEBS J. 274

      Pages: 137-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Molecular cloning of a cDNA encoding mouse D-aspartate oxidase and functional characterization of its recombinant proteins by site-directed mutagenesis2007

    • Author(s)
      Katane, Masumi
    • Journal Title

      Amino Acids 32

      Pages: 69-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ubiquitin-conjugating enzyme Cdc34 mediates cadmium resistance in budding yeast through ubiquitination of the transcription factor Met42007

    • Author(s)
      Gi-Wook, Hwang
    • Journal Title

      Biochem.Biophys.Res.Commun 363

      Pages: 873-878

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Role of isomerized protein repair enzyme,PIMT,in cellular functions (Review)2007

    • Author(s)
      Furuchi, Takemitsu
    • Journal Title

      Yakugaku Zasshi 127

      Pages: 1927-1936

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] Caenorhabditis elegans has two genes encoding functional d-aspartate oxidases2007

    • Author(s)
      Katane, M., Seida, Y., Sekine, M., Furuchi, T., Homma, H
    • Journal Title

      FEBS J 274(1)

      Pages: 137-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Molecular cloning of a cDNA encoding mouse D-aspartate oxidase and functional characterization of its recombinant proteins by site-directed mutagenesis2007

    • Author(s)
      Katane, M., Furuchi, T., Sekine, M., Homma, H
    • Journal Title

      Amino Acids 32(1)

      Pages: 69-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ubiquitin-conjugating enzyme Cdc34 mediates cadmium resistance in budding yeast through ubiquitination of the transcription factor Met42007

    • Author(s)
      Hwang, GW., Furuchi, T., Naganuma, A
    • Journal Title

      Biochem Biophys Res Commun 363(3)

      Pages: 873-878

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of isomerized protein repair enzyme, PIMT, in cellular functions2007

    • Author(s)
      Furuchi, T., Homma, H
    • Journal Title

      Yakugaku Zasshi 127(12)

      Pages: 1927-1936

    • NAID

      110006546568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ubiquitin-conjugating enzyme Cdc34 mediates cadmium resistance in budding yeast through ubiquitination of the transcription factor Met4.2007

    • Author(s)
      Gi-Wook, Hwang
    • Journal Title

      Biochem.Biophys.Res.Commun. 363

      Pages: 873-878

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caenorhabditis elegans has two genes encoding functional D-aspartate oxidases.2007

    • Author(s)
      Katane, Masumi
    • Journal Title

      FEBS J. 274(1)

      Pages: 137-149

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Molecular cloning of a cDNA encoding mouse D-aspartate oxidase and functional characterization of its recombinant proteins by site-directed mutagenesis.2007

    • Author(s)
      Katane, Masumi
    • Journal Title

      Amino Acids 32

      Pages: 69-78

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells2006

    • Author(s)
      Takahashi, Tsutomu
    • Journal Title

      Cancer Res 66

      Pages: 11932-11937

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells2006

    • Author(s)
      Takahashi, T., Furuchi, T., Naganuma, A
    • Journal Title

      Cancer Res 66(24)

      Pages: 11932-11937

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells.2006

    • Author(s)
      Takahashi, Tsutomu
    • Journal Title

      Cancer Res. 66(24)

      Pages: 11932-11937

    • Related Report
      2006 Annual Research Report
  • [Presentation] Protein L-isoaspartyl(D-aspartyl)methyltransferase(PIMT)のプロモーター領域の解析2008

    • Author(s)
      小杉 桜子
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of promoter region of Protein L-isoaspartyl(D-aspartyl)methyltransferase gene2008

    • Author(s)
      Kosugi, S
    • Organizer
      The 128th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Protein L-isoaspartyl(D-aspartyl)methyltransferase(PIMT)のプロモーター領域の解析2008

    • Author(s)
      小杉 桜子
    • Organizer
      日本薬学会 第128年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-03-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] Protein L-isoaspartyl/D-aspartyl methyltransferase(PIMT)の転写調節機構の解析2007

    • Author(s)
      古地 壯光
    • Organizer
      日本生化学、日本分子生物学会合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanisms of transcriptional regulation of Protein L-isoaspartyl/D-aspartyl methyltransferase gene in HEK293 cells2007

    • Author(s)
      Furuchi, T
    • Organizer
      The 80th Annual meeting of the Japanese Biochemical Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Protein L-isoaspartyl/D-aspartyl methyltransferase(PIMT)の転写調節機構の解析2007

    • Author(s)
      古地 壯光
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] タンパク質異性化修復酵素PIMTの発現調節機構の解析2007

    • Author(s)
      小杉 桜子
    • Organizer
      第3回D-アミノ酸研究会学術講演会
    • Place of Presentation
      徳島
    • Year and Date
      2007-09-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 異性化タンパク質修復酵素PIMTの細胞機能における役割2007

    • Author(s)
      古地 壯光
    • Organizer
      日本薬学会第127年会
    • Place of Presentation
      富山
    • Year and Date
      2007-03-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Role of isomerized protein repair enzyme, PIMT, in cellular functions2007

    • Author(s)
      Furuchi, T
    • Organizer
      The 127th Annual Meeting of the Pharmaceutical Society of Japan
    • Place of Presentation
      Toyama
    • Year and Date
      2007-03-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanisms of protein L-isoaspartyl/D-aspartyl methyltransferase(PIMT)expression in HEK293 cells2006

    • Author(s)
      Kosugi, S
    • Organizer
      The 3rd Annual meeting of D-Amino Acid Research Society
    • Place of Presentation
      Tokushima
    • Year and Date
      2006-09-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] タンパク質異性化修復酵素の発現抑制による増殖刺激に対する細胞応答性の変化2006

    • Author(s)
      小杉 桜子
    • Organizer
      第2回D-アミノ酸研究会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2006-09-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alteration of cell response to growth stimulus by silencing of isomerized protein repair enzyme2006

    • Author(s)
      Kosugi, S
    • Organizer
      The 2nd Annual meeting of D-Amino Acid Research Society
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-09-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of protein repair enzyme results in impairment of EGF-stimu lated MEK-ERK signaling2006

    • Author(s)
      Kosugi, Sakurako
    • Organizer
      20th International Congress on Biochemistry and Molecular Biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of protein repair enzyme results in impairment of EGF-stimulated MEK-ERK signaling2006

    • Author(s)
      Kosugi, S
    • Organizer
      20th International Congress on. Biochemistry and Molecular Biology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.pharm.kitasato-u.ac.jp/ac/web/ResTop.htm

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.pharm.kitasato-u.ac.jp/ac/web/ResTop.htm

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] siRNA発現ベクター及びそれを用いて作製したPIMT発現抑制株2005

    • Inventor(s)
      本間 浩, 古地 壯光, 小杉 桜子
    • Industrial Property Rights Holder
      学校法人北里学園
    • Industrial Property Number
      2005-112635
    • Filing Date
      2005-04-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] siRNA発現ベクター及びそれを用いて作製したPIMT発現抑制株2005

    • Inventor(s)
      本間 浩, 古地 壯光, 小杉 桜子
    • Industrial Property Rights Holder
      学校法人北里学園
    • Filing Date
      2005-04-08
    • Acquisition Date
      2006-10-26
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi