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Functional analysis of a novel GTP-binding protein involved in apoptosis.

Research Project

Project/Area Number 12480213
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

INOUE Jun-ichiro  Fac. Sci & Tech. Keio Univ. Professor, 理工学部, 教授 (70176428)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsGTP-binding protein / Cell cycle / Apoptosis / RNP K homology domain / RNA-binding / protein, DT40 / 細胞増殖 / アポートシス / 遺伝子破壊 / Gタンパク質 / 翻訳後修飾
Research Abstract

We have cloned cDNAs encoding the entire coding region of a human homologue (H-ERA) and a mouse homologue (M-ERA) of ERA. The mammalian homologue of ERA consists of a typical GTPase/GTP-binding domain and a putative K homology (KH) domain, which is known as an RNA binding domain. We performed transfection experiments with wild-type H-ERA or various H-ERA mutants. H-ERA possessing the amino acid substitution mutation into the GTPase domain induced apoptosis of HeLa cells, which was blocked by Bcl-2 expression. Deletion of the C-terminus, which contains a part of the KH domain, alleviated apoptosis by the H-ERA mutant, suggesting the importance of this domain in the function of H-ERA. We have also shown the RNA binding activity of H-ERA by pull-down experiments using RNA homopolymer immobilized on beads or recombinant H-ERA proteins. Thus, H-ERA may play an important role in the regulation of apoptotic signalling with its GTPase/GTP binding domain. To elucidate the physiological function of eukaryotic ERA, we have performed a genetic analysis of chicken ERA (GdERA) in DT40 cells. Depletion of GdERA diminished the growth rate of the cells, accompanied by an accumulation of apoptotic cells. The analysis of cell cycle indicates that the elimination of GdERA caused arrest at G1 phase, but not at M phase, which highlights the distinct role of vertebrate ERA in the cell cycle progression compared to prokaryotic ERA. Furthermore, human ERA (HsERA) rescued the phenotype of GdERA-deficient cells, whereas a mutant of HsERA deprived of RNA binding activity did not. These data suggest that vertebrate ERA regulates the G1 phase progression via an as yet unknown molecular mechanism, which involves RNA recognition by ERA.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Taishin Akiyama: "Mammalian homologue of E.coli ras-like GTPase (ERA) is a possible apoptosis regulator with RNA binding activity"Genes to Cells. 6. 987-1001 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin Gohda: "Elimination of the vertebrate Escherichia coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis"Oncogene. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taishin Akiyama: "Mammalian homologue of E.coli ras-like GTPase (ERA) is a possible apoptosis regulator with RNA binding activity"Genes to Cells. 6. 987-1001 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin Gohda: "Elimination of the vertebrate Escherichia coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis"Oncogene. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiyama, T: "Mammalian homologue of E.Ras-like GTPase(ERA) is a possible apoptosis regulator with RNA binding activity"Cenes Cells. 6. 987-1001 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi,N.: "Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis"EMBO JOURNAL. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sharma,K.M.: "Aurine Tricarboxylic Acid, a potent metal-chelating inhibitor of NFκB-DNA binding."Bioorg.Med.Chem. 8. 1819-1823 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hatzoglou,A.: "Tumor necrosis factor receptor family member BCMA (B-cell maturation) associates with TRAF1, TRAF2 and TRAF3 and activates NF-kB, Elk-1 and c-Jun N-terminal kinase."J.Immunol. 165. 1322-1330 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsumoto,N.: "Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C."Bioorg.Med.Chem.Lett.. 10. 865-869 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inoue,J.: "Tumor necrosis factor receptor-associated factor (TRAF) family : adapter proteins that mediate cytokine signaling."Exp.Cell Res. 254. 14-24 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 井上純一郎: "TRAF6シグナルの生理的役割"Molecular Medicine. Vol.37. 110-117 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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