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Elucidation of a novel role of N-glycan by the analysis of the ubiquitin ligases that recognize sugar chain.

Research Project

Project/Area Number 17580088
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied biochemistry
Research InstitutionTOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH

Principal Investigator

YOSHIDA Yukiko  Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (90271543)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsF-box protein / ubiquitin ligase / N-glycan / ER-associated degradation / chaperone
Research Abstract

We found an ubiquitin ligase, SCF^<Fbs1>, which recognizes N-glycans in glycoproteins. When the endoplasmic reticulum (ER)-resident newly synthesized proteins are not folded properly, they are degraded through the ER-associated degradation (ERAD) pathway. The analysis of substrates of SCF^<Fbs1> has shown that SCF^<Fbs1> is involved in the ERAD pathway. Other than Fbs1, at least four F-box proteins (Fbs2, Fbg3-5) that show high homology in the substrate-binding domain (SBD) have been reported. However, it remains to be established whether Fbg3,4, and 5 proteins bind specific N-glycans and what are their substrates. In this study, we have tried to elucidate the roles of Fbs1 homologs in vivo.
Although the amino acid identity in SBD between Fbs2 and Fbg3 proteins and between Fbg4 and Fbg5 proteins display more than 60%, only Fbs2 and Fbg5 have the ability to bind N-glycans as well as Fbs1. We have identified the proteins that interact to F-box proteins by using TOF-MS.
We show that the in vivo majority of Fbs1 is present as Fbs1-Skp1 heterodimers but not SCF complex. Moreover, Fbs1 prevented the aggregation of the glycoproteins in vivo and in vitro. Fbs1 is present abundantly in the nervous system, and Fbs1 assists clearance of aberrant glycoproteins in neuronal cells by suppressing aggregates formation, independent of ubiquitin ligase activity, and thus functions as a unique chaperone for those proteins.

Report

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

    (13 results)

All 2007 2006 2005

All Journal Article (13 results)

  • [Journal Article] A neural-specific F-box protein Fbsl functions as a chaperone suppressing glycoprotein aggregation.2007

    • Author(s)
      Y.Yoshida, et al.
    • Journal Title

      J.Biol.Chem. 282

      Pages: 7137-7144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structural basis for the selection of glycosylated substrates by SCF^<Fbsl> ubiquitin ligase.2007

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

      Proc.Nat. Acad.Sci.U.S.A. 104

      Pages: 5777-5781

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A neural-specific F-box protein Fbs1 functions as a chaperone suppressing glycoprotein aggregation2007

    • Author(s)
      Yoshida, Y., Murakami, A., Iwai, K., Tanaka, K.
    • Journal Title

      J.Biol.Chem. 282

      Pages: 7137-7144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structural basis for the selection of glycosylated substrates by SCFFbs1 ubiquitin ligase.2007

    • Author(s)
      Mizushima, T., Yoshida, Y., Hirao, Kumanomidou, T., Hasegawa, Y., Suzuki, A., Yamane, T., Tanaka, K.
    • Journal Title

      Proc.Nat.Acad.Sci.U.S.A. 104

      Pages: 5777-5781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A neural-specific F-box protein Fbsl functions as a chaperone suppressing glycoprotein aggregation.2007

    • Author(s)
      Y.Yoshida, et al.
    • Journal Title

      J. Biol. Chem. 282・10

      Pages: 7137-7144

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structural basis for the selection of glycosylated substrates by SCF^<FbSl> ubiquitin ligase.2007

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

      Proc.Nat.Acad.Sci.U.S.A. 104・14

      Pages: 5777-5781

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 小胞体関連分解(ERAD)とュビキチン系2006

    • Author(s)
      吉田 雪子
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 1292-1297

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 小胞体関連分解(ERAD)とユビキチン系2006

    • Author(s)
      吉田 雪子
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 1292-1297

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Glycoprotein-specific ubiquitin-ligases recognize N-glycans in unfolded substrates.2005

    • Author(s)
      Y.Yoshida, et al.
    • Journal Title

      EMBO Reports 3

      Pages: 239-244

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 小胞体関連分解のメカニズム2005

    • Author(s)
      吉田雪子
    • Journal Title

      炎症と免疫 13

      Pages: 246-254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression and assay of glycoprotein-specific ubiquitin-ligases.2005

    • Author(s)
      Y.Yoshida
    • Journal Title

      Methods in Enzymology 398

      Pages: 159-169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded subsrates.2005

    • Author(s)
      Yoshida, Y., Adach, E., Fukiya, K., Iwai, K., Tanaka, K.
    • Journal Title

      EMBO reports 6

      Pages: 239-244

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression and assay of glycoprotein-specific ubiquitin ligases.2005

    • Author(s)
      Yoshida. Y
    • Journal Title

      the Ubiquitin-Proteasome System' Methods in Enzymology (Eds.by Deshaies, R.J., Hershko, A., Jentsch, S., Pickart, S., Tanaka, K.) (Academic Press) 398

      Pages: 159-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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