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

Functional analyses of ER stress sensor proteins

Research Project

Project/Area Number 13480239
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionNARA INSTITUTE OF SCIENCE AND TECHNOLOGY

Principal Investigator

KOHNO Kenji  Nara Institute of Science & Technology, Research & Education Center for Genetic Information, Professor, 遺伝子教育研究センター, 教授 (50142005)

Co-Investigator(Kenkyū-buntansha) TSURU Akio  NAIST, Res. & Edu. Ctr for Genet. Inf., Instructor, 遺伝子教育研究センター, 助手 (80273861)
KIMATA Ykio  NAIST, Res. & Edu. Ctr for Genet. Inf., Instructor, 遺伝子教育研究センター, 助手 (60263448)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
KeywordsER stress / Unfolded Protein Response / IRE1 / BiP / transport vesicle / ストレスセンサー / マイクロアレイ / 28srRNA
Research Abstract

1. The accumulation of unfolded proteins in the endoplasmic reticulum (ER) induces a transcriptional response in the nucleus, leading to the upregulation of many ER-resident proteins involved in protein folding, to protect cells from ER stress. This response is called the unfolded protein response (UPR), which is essential for maintaining the ER homeostasis. Two important factors for UPR have been identified. One is an ER stress sensor protein Ire1, and the other is a transcription factor Hac1. Overexpression of IRE1 or HAC1 specifically suppressed growth defects of sec mutants defective in COPII vesicle formation. These findings suggest that the activation of the UPR affects ER-to-Golgi transport via stimulation of COPII vesicle formation from the ER.
Induction of UPR needs the activation of Ire1. It was previously hypothesized that BiP/Kar2 plays a direct role in the signaling mechanism. In this model, association of BiP/Kar2 with Ire1 represses the UPR pathway while under conditions of ER stress, BiP/Kar2 dissociation leads to activation. To test this model, we analyzed five temperature-sensitive alleles of the yeast KAR2 gene. When cells carrying a mutation in the Kar2 substrate-binding domain were incubated at the restrictive temperature, association of Kar2 to Ire1 was disrupted, and the UPR pathway was activated even in the absence of extrinsic ER stress. Conversely, cells carrying a mutation in the Kar2 ATPase domain, in which Kar2 poorly dissociated from Ire1 even in the presence of tunicamycin, a potent inducer of ER stress, were unable to activate the pathway. Our findings provide strong evidence in support of BiP/Kar2-dependent Ire1 regulation model and suggest that Ire1 associate with Kar2 as a chaperone substrate.

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Iwawaki, T.: "Translational control by ER transmembrane kinase/ribonuclease IRE1 under ER stress"Nature Cell Biol.. 3. 158-164 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koizumi, N.: "Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum located transmembrane protein kinases"Plant Physiol.. 127. 949-962 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okushima, Y.: "Isolation and characterization of a putative transducer of endoplasmic reticulum stress in Orzya sativa"Plant Cell Physiol.. 43. 532-539 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashio, H.: "A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum"Biochem.Biophys.Res.Commun.. 296. 568-574 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hsoda, A.: "JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J domain and thioredoxin-like motifs"J.Biol.Chem.. 278. 2669-2676 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimata, Y.: "Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins"Mol.Biol.Cell. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwawaki, T.: "Translational control by ER transmembrane kinase/ribonuclease IRE1 under ER stress"Nature Cell Biol.. 3. 158-164 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koizumi, N.: "Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum located transmembrane protein kinases"Plant Physiol.. 127. 949-962 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okushima, Y.: "Isolation and characterization of a putative transducer of endoplasmic reticulum stress in Oryza sativa"Nature Cell Biol.. 43. 532-539 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashio, H.: "A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum"Biochem. Biophys. Res. Commun.. 296. 568-574 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hosoda, A.: "JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J domain and thioredoxin-like motifs"J. Biol. Chem.. 278. 2669-2676 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimata,Y.: "Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins"Mol. Biol. Cell in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimata, Y.: "Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins"Mol. Biol. Cell. 14(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashio, H.: "A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum"Biochem. Biophys.. 296. 568-574 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okushima, Y.: "Isolation and characterization of a putative transducer of endoplasmic reticulum stress in Oryza sativa"Plant Cell Physiol.. 43. 532-539 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwawaki, Hosoda, Okuda, Kamigori, Nomura, Kimata, Tsuru, Kohno: "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress"Nature Cell Biology. 3. 158-164 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 都留秋雄, 河野憲二: "小胞体ストレス応答に関与する膜キナーゼの機能"細胞工学. 21(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩脇隆夫, 河野憲二: "小胞体ストレスにおけるIRE1による翻訳抑制"実験医学. 19. 981-983 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi