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Expression and Regulation of Steroidogenic P-450s in Animal Organs

Research Project

Project/Area Number 02044112
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

OMURA Tsuneo  Kyushu University, Graduate School of Medical Science, Professor, 大学院医学系研究科, 教授 (80029933)

Co-Investigator(Kenkyū-buntansha) ZANGER Ulrich M.  Universitat Basel, Biozentrum, Research Associate, バイオセンター, 研究員
WALTER Peter  University of California San Francisco, Medical School, Professor, 医学部, 教授
VON HEIJNE Gunnar  Karolinska Institute, Department of Molecular Biology, Associate Prof., 準教授
PARKER Keith L.  Duke University, Medical Center, Professor, 医学部, 教授
WATERMAN Mic  バンデルビルト大学, 医学部, 教授
SAKAGUCHI Masao  Kyushu University, Graduate School of Medical Science, Instructor, 大学院医学系研究科, 助手 (30205736)
MOROHASHI Ken-ichirou  Kyushu University, Graduate School of Medical Science, Instructor, 大学院医学系研究科, 助手 (30183114)
ITO Akio  Kyushu University, Faculty of Science, Professor, 理学部, 教授 (30037379)
MIHARA Katsuyoshi  Kyushu University, Graduate School of Medical Science, Associate Professor, 大学院医学系研究科, 助教授 (40029963)
WATERMAN Michael R.  Vanderbilt University, School of Medicine, Professor
WALTER P.  カリフォルニア大学, 医学部, 教授
ZANGER U.  テキサス大学, 医学部, 研究員
WATERMAN M.R  テキサス大学, 医学部, 教授
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 1992: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1990: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsCytochrome P-450 / Steroid Hormone Biosynthesis / Gene Expression / Biosynthesis of Cytochrome P-450 / Pー450 / Pー450の生合成
Research Abstract

Six forms of cytochrome P-450, three mitochondrial and three microsomal P-450s, participate in the biosynthesis of steroid hormones in animal organs. This research was designed to investigate the basic mechanism regulating the expression of these steroidogenic P-450s in the cells, and focused on the following two topics.
1. Regulation of expression of steroidogenic P-450 genes.
The main object of the research was the regulation of P-450(11beta), which expresses only in adrenal cortex cells. P-450(SCC), which expresses in all steroidogenic organs, was also examined for comparison. The research was carried out in collaboration with Dr.M.R.Waterman (University of Texas) and Dr.K.L.Parker (Duke University).
Four cis-acting elements, Ad1-Ad4, were identified in the promoter region of P-450(11beta). A protein factor binding to Ad4 was purified from the nuclear extract of adrenal cortex cells, and its amino acid sequence was deduced from the cloned cDNA. Ad4 is present in the promoter region of all steroidogenic P-450s including P-450(SCC) and Ad4BP expresses only in steroidogenic organs. Ad4-Ad4B& system seems to be functional in the expression of steroidogenic P-450s in steroid hormone-producing. cells.
2. Integration of P-450 proteins into microsomal and mitochondrial membranes.
The main object of the research was the mechanism of correct integration of newly synthesized P-450 molecules into the membrane of endoplasmic reticulum. The research was carried out in collaboration with Dr.P.Walter (University of California) and Dr.G. von Heijne (Karolinska Institute).
The function of the amino-terminal signal anchor sequence of P-450 molecule in the integration of newly synthesized molecules was analyzed by the introduction of amino acid mutations into the sequence. The correct insertion of the amino terminal sequence was dependent on the balance between the electric charge at the amino temrinus and the hydrophobicity of the following sequence.

Report

(3 results)
  • 1992 Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Ken-ichirou MOROHASHI: "Enzymatic Activities of P-450(11B)s Expressed by Two cDNAs in COS-7 Cells." J.Biochem.107. 635-640 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takashi SATO: "The Amino-terminal Structures That Determine Topological Orientation of Cytochrome P-450 in Microsomal Membrane." EMBO J.9. 2391-2397 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] TomoKo KUROIWA: "Structural Requirements for Interruption of Protein Trans-location across Rough Endoplasmic Reticulum Membrane." J.Biochem.108. 829-834 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shirou KIRITA: "Structural Analysis of Multiple Bovine P-450(11B) Genes and Their Promotor Activities." J.Biochem.108. 1030-1041 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shin-ichirou HONDA: "Novel cAMP Regulatory Elements in the Promotor Region of Bovine P-450(11B) Gene." J.Biochem.108. 1042-1049 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ken-ichirou MOROHASHI: "Tissue-Specific Transcription of P-450(11B) Gene In Vitro." J.Biochem.108. 1050-1056 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tomoko KUROIWA: "Systematic Analysis of Stop-Transfer Sequence for Micro-somal Membrane." J.Biol.Chem.266. 9251-9255 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masao SAKAGUCHI: "Yeast Gene Which Suppresses the Defect in Protein Export of a secY Mutant of E.Coli." J.Biochem.109. 799-802 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeki FURUYA: "Cytosolic and Mitochondrial Surface Factor-independent Import of a Synthetic Peptide into Mitochondria." EMBO J.10. 1759-1766 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masao SAKAGUCHI: "Functions of Signal and Signal-Anchor Sequences Are Determined by the Balance between the Hydrophobic Segment and the N-terminal Charge." Proc.Natl.Acad.Sci.USA. 89. 16-19 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Jun IWAHASHI: "Characterization of Adrenodoxin Precursor Expressed in Escherichia coli." J.Biochem.111. 451-455 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ken-ichirou MOROHASHI: "A Common trans-Acting Factor,Ad4-binding Protein,to the Promoters of Steroidogenic P-450s." J.Biol.Chem.267. 17913-17919 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masao SAKAGUCHI: "Mitochondrial Porin Can Be Translocated across Both Endoplasmic Reticulum and Mitochondrial Membranes." J.Biochem.112. 243-248 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tosihide HASHIMOTO: "Cooperative Transcription Activation between Adl,a CRE-Like Element,and Other Elements in the CYP11B Gene Promoter." J.Biochem.112. 573-575 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masatoshi NOMURA: "Three Forms of Rat CYP11B Genes:11B-Hydroxylase Gene,Aldosterone Synthase Gene,and a Novel Gene." J.Biochem.113. 144-152 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ken-ichirou Morohashi: "Enzymatic Activities of P-450(11BETA)s Expressed by Two cDNAs in COS-7 Cells." J. Biochem.107. 635-640 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takashi Sato: "The Amino-terminal Structures That Determine Topological Orientation of Cytochrome P-450 in Microsomal Membrane." EMBO J.9. 2391-2397 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tomoko Kuroiwa: "Structural Requirements for Interruption of Protein Translocation across Rough Endoplasmic Reticulum Membrane." J. Biochem.108. 829-834 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shirou Kirita: "Structural Analysis of Multiple Bovine P-450(11BETA) Genes and Their Promoter Activities." J. Biochem.108. 1030-1041 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shin-ichirou Honda: "Novel cAMP Regulatory Elements in the Promoter Region of Bovine P-450(11BETA) Gene." J. Biochem.108. 1042-1049 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ken-ichirou Morohashi: "Tissue-Specific Transcription of P-450(11BETA) Gene In Vitro." J. Biochem.108. 1050-1056 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tomoko Kuroiwa: "Systematic Analysis of Stop-Transfer Sequence for Microsomal Membrane." J. Biol. Chem.266. 9251-9255 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masao Sakaguchi: "Yeast Gene Which Suppresses the Defect in Protein Export of a secY Mutant of E.Coli." J. Biochem.109. 799-802 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shigeki Furuya: "Cytosolic and Mitochondrial Surface Factor-independent Import of a Synthetic Peptide into Mitochondria." EMBO J.10. 1759-1766 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masac Sakaguchi: "Functions of Signal and Signal-Anchor Sequences Are Determined by the Balance between the Hydrophobic Segment and the N-terminal Charge." Proc. Natl. Acad. Sci. USA. 89. 16-19 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Jun Iwahashi: "Characterization of Adrenodoxin Precursor Expressed in Escherichia coli." J. Biochem.111. 451-455 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ken-ichirou Morohashi: "Common trans-Acting Factor, Ad4-binding Protein, to the Promoters of Steroidogenic P-450s." J. Biol. Chem.267. 17913-17919 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masao Sakaguchi: "Mitochondrial Porin Can Be Translocated across Both Endoplasmic Reticulum and Mitochondrial Membranes." J. Biochem.112. 243-248 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshihide Hashimoto: "Cooperative Transcription Activation between Ad1, a CRE-Like Element, and Other Elements in the CYP11BETA Gene Promoter." J. Biochem.112. 573-575 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Masatoshi Nomura: "Three Forms of Rat CYP11BETA Genes : 11BETA-Hydroxylase Gene, Aldosterone Synthase Gene, and a Novel Gene." J. Biochem.113. 144-152 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tomoko Kuroiwa: "Systematic Analysis of Stop-Transfer Sequence for Microsomal Membrane" J.Biol.Chem.266. 9251-9255 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shigeki Furuya: "Cytosolic and Mitochondrial Surface Factor-independent Import of a Synthetic Peptide into Mitochondria" EMBO J.10. 1759-1766 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masao Sakaguchi: "Functions of Signal and Signal-Anchor Sequences Are Determined by the Balance between the Hydrophobic segment and the N-terminal Charge" Proc.Natl.Acad.Sci.USA. 89. 16-19 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 山本 尚三: "リピドバイオファクタ-" 化学同人, 197 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sato,T.: "The Aminoーterminal Structure That Determine Topological Orientation of Cytochrome Pー450 in Microsomal Membrane." EMBO Journal. 9. 2391-2397 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Morohashi,K.: "Enzymatic Activities of Pー450(11β) Expressed by Two cDNAs in COSー7 Cells." Journal of Biochemistry. 107. 635-640 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kuroiwa,T.: "Structural Requirements for Interruption of Protein Translocation across Rough Endoplasmic Reticulum Membrane." Journal of Biochemistry. 108. 829-834 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ishihara,S: "Molecular Cloning and Sequence Analysisof cDNA Coding for Rat Liver Hemoprotein Hー450" Journal of Biochemistry. 108. 899-902 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kirita,S.: "Structural Analysis of Multiple Bovine Pー450(11β) Genes and Their Promotor Activities." Journal of Biochemistry. 108. 1030-1041 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Honda,S.: "Novel cAMP Regulatory Elements in the Promotor Region of Bovine Pー450(11β) Gene." Journal of Biochemistry. 108. 1042-1049 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Morohashi,K.: "Tissueーspecific Transcription of Pー450(11β) Gene In Vitro." Journal of Biochemistry. 108. 1050-1056 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Emi,Y.: "A Different Cytochrome Pー450 Form Is Induced in Primary Cultures of Rat Hepatocytes." Proceedings of National Academy of Science USA. 87. 9746-9750 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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