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Analysis on the mechanism of ER membrane proliferation upon ER protein overproduction in yeast

Research Project

Project/Area Number 10460034
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionThe University of Tokyo

Principal Investigator

OHTA Akinori  Univ. Tokyo, Dept. Biotech., Professor, 大学院・農学生命科学研究科, 教授 (30125885)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordsendoplasmic reticulum / Saccharomyces cerevisiae / Candida maltosa / cytochrome P450A1k / ER proliferation / phospholipid / IRE1 / ER membrane / cytochrome P45Alk
Research Abstract

Endoplasmic reticulum (ER) is the center of secretory protein and lipid syntheses in eukaryotic cells. Although it has been attracted many researchers who are interested in those biosynthetic pathways, its proliferation and biogenesis are not yet well understood. We overproduced an ER membrane protein cytochrome P450Alk1 of Candida maltosa in Saccharomyces cerevisiae and analyzed the mechanism of the resultant ER proliferation, especially in the aspects of ER chaperone induction and membrane lipid metabolism. The results are; 1) There is no enhanced synthesis of membrane phospholipids during ER proliferation. 2) The requirement of Ire1p for ER proliferation is dependent on the genetic backgrounds of employed yeast strains. 3) Degradation of ER misfolded proteins does not necessarily occur by the proteasome system. 4) We established a system where yeast growth is dependent on the externally-supplied phospholipids. This enables us to analyze membrane lipid metabolism during ER protein-induced ER proliferation.

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Yon, J-O, Nakamura, H. al.: "Incorporation of extracellular phospholipids and their effect on the growth and lipid the Saccharomyces cerevisiae cho1/pss mutant"Biochimica Biophysica et Acta. 1394. 23-28 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Umebayasi, K., Hirata, H et al.: "Unfolded protein response-induced BiP/Kar2p production protects cell growth against accumulation of misfolded protein aggregates in the yeast endoplasmic reticulum"European Journal of Cell Biology. 78. 726-738 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takewaka, T., Zimmer, T et al.: "Null mutation in IRE1 gene inhibits Overproduction of microsome P45OAIk1 proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae"Journal of Biochemistry. 125. 507-514 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zimmer, T., Ogura, A., et al.: "Misfolded membrane-bound cytochrome P450 activates KAR2 induction through two mechanisms"Journal of Biochemistry. 126. 1080-1089 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura, H., Miura, K et al.: "Phosphatidylserine synthesis required for the maximal tryptophan transport activity Saccharomyces cerevisiae"Biosci. Biotechnol. Biochem.. 64. 167-172 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zimmer, T., Ogura, A., et al.: "Gene regulation in response to overexpression of cytochrome P450 and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae"Biosci. Biotechnol. Biochem.. 64. 1930-1936 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Umebayasi, K., Fukuda, R., et al.: "Activation of the Ras-cAMP signal transductionpathway inhibits the proteasome-independent degradation of misfolded protein aggregates in the ER lumen"J. Biol. Chem.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriya Ohkuma, Thomas Zimmer, Toshiya lida, Wolf-Hagen Schunck, Akinori Ohta, and Masamichi Takagi: "Isozyme function of n-alkane-inducible cytochrome P450 in Candida maltosa revealed by sequential gene disruption."J. Biol. Chem.. 273. 3948-3953 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Thomas Zimmer, Toshiya lida, Wolf-Hagen Schunck, Yuzo Yoshida, Akinori Ohta, and Masamichi Takagi: "Relation between evolutionary distance and enzymatic properties among the members of the CYP52A subfamily of Candida maltosa"Biochem. Biophys. Res. Commun.. 251. 244-247 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jei-Oh Yon, Hidemitsu Nakamura, Akinori Ohta, and Masamichi Takagi: "Incorporation of extracellular phospholipids and their effect on the growth and lipid metabolism of the Saccharomyces cerevisiae"Biochim. Biophys. Acta. 1394. 23-32 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuyoshi Takawaka, Thomas Zimmer, Aiko Hirata, Akinori Ohta, and Masamichi Takagi: "Null mutation in IRE1 gene inhibits overproduction of microsomal cytochrome P450Alk1 (CYP52A3) and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae."J. Biochem.. 125. 507-514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyouhei Umebayashi, Aiko Hirata, Hiroyuki Horiuchi, Akinori Ohta, and Masamichi Takagi: "Unfolded protein response-induced BiP/Kar2p production protects cell growth against accumulation of misfolded protein aggregates in the yeast endoplasmic reticulum."Eur. J. Cell Biol.. 78. 726-738 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Thomas Zimmer, Atsushi Ogura, Akinori Ohta, and Masamichi Takagi: "Misfolded membrane-bound cytochrome P450 activates KAR2 induction through two distinct mechanisms"J. Biochem.. 126. 1080-1089 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hidemitsu Nakamura, Keiji Miura, Yu Fukuda, Isao Shibuya, Akinori Ohta, and Masamichi Takagi: "Phosphatidylserine synthesis required for the maximal tryptophan transport activity in Saccharomyces cerevisiae."Biosci. Biotech. Biochem.. 64. 167-172 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Thomas Zimmer, Atsushi Ogura, Tsuyoshi Takewaka, Rose-Marie Zimmer, Akinori Ohta, and Masamichi Takagi: "Gene regulation in response to over expression of cytochrome P450 and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae."Biosci. Biotechnol. Biochem.. 64. 1930-1936 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyouhei Umebayashi, Ryouichi Fukuda, Aiko Hirata, Hiroyuki Horiuchi, Akihiko Nakano, Akinori Ohta, and Masamichi Takagi: "Activation of the Ras-cAMP signal transduction pathway inhibits the proteasome-independent degradation of misfolded protein aggregates in the ER lumen"J. Biol. Chem.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yon,J-O,Nakamura,H. et al.: "Incorporation of extracellular phospholipids and their effect on the growth and lipid Saccharomyces cerevisiae chol/pss mutant."Biochimica Biophysica et Acta. 1394. 23-28 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Umebayasi,K.,Hirata,A., et al.: "Unfolded protein response-induced BiP/Kar2p production protects cell growth against accumu protein aggregates in the yeast endoplasmic reticulum."European Journal of Cell Biology. 78. 726-738 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takewaka,T.,Zimmer,T., et al.: "Null mutation in IRE1 gene inhibits Overproduction of microsome P450Alk1 (CYP52A3) and endoplasmic reticulum in Saccharomyces cerevisiae"Journal of Biochemistry. 125. 507-514 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zimmer,T.,Ogura,A., et al al.: "Misfolded membrane-bound cytochrome P450 activates KAR2 induction through two distinct mechanisms"Journal of Biochemistry. 126. 1080-1089 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura,H.,Miura,K., et et al: "Phosphatidylserine synthesis required for the maximal tryptophan transport activity in Saccharomyces cerevisiae"Biosci.Biotechnol.Biochem.. 64. 167-172 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zimmer,T.,Ogura,A., et al.: "Gene regulation in response to overexpression of cytochrome P450 and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae."Biosci.Biotechnol.Biochem.. 64. 1930-1936 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yon,J-O,Nakamura,H.et al.: "Incorporation of extracellular phospholipids and their effect on the growth and lipid metabolism of the Saccharomyces cerevisiae cho1/pss mutant"Biochimica Biophysica et Acta. 1394. 23-32 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Umebayasi,K.,Hirata,A.,et al.: "Unfolded protein response-induced BiP/Kar2p production protects cell growth against accumulation of misfolded protein aggregates in the yeast endoplasmic reticulum"European Journal of Cell Biology. 78. 726-738 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takewaka,T.,Zimmer,T.,et al.: "Null mutation in IREI gene inhibits Overproduction of microsome P450AIkl (CYP52A3) and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae"Journal of Biochemistry. 125. 507-514 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zimmer,T.,Ogura,A.,et al.: "Misfolded membrane-bound cytochrome P450 activates KAR2 induction through two distinct mechanisms"Journal of Biochemistry. 126. 1080-1089 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,H.,Miura,K.,et al.: "Phosphatidylserine synthesis required for the maximal tryptophan transport activity in Saccharomyces cerevisiae"Bioscience,Biotechnology,and Biochemistry. 64. 167-172 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yon, J-O, Nakamura, H.et al.: "Incorporation of extracellular phospholipids and their effect on the growth and lipid metabolism of the Saccharomyces cerevisiae cho1/pss mutant." Biochimica Biophysica et Acta. 1394. 23-32 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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