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Regulation and Pathology of Gene Expression of Intracellular Proteases Science, Dept. Mol. Biol., Director

Research Project

Project/Area Number 63304034
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

SUZUKI Koichi  Tokyo Metropolitan Institute of Medical, 遺伝子情報部, 部長 (80011948)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Kenji  Univ. Tokyo, Dept. SCience, Prof., 理学部・生物雑学科, 教授 (70011533)
ICHIHARA Akira  Univ. Tokushima, Enzyme Inst. Prof., 酵素科学センター, 教授 (20035405)
SUGITA Hideo  Natl. Inst. Neurology, President, 所長 (80009951)
KATO Keitaro  Univ. Kyushu, Dept. Pharmacol., Prof., 薬学部, 教授 (70037571)
KATUNUMA Nobuhiko  Univ. Tokushima, Enzyme Inst., Prof., 酵素科学センター, 教授 (50035375)
村地 孝  京都大学, 医学部, 教授 (10089104)
佐々木 實  名古屋市立大学, 医学部, 教授 (10080003)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥21,100,000 (Direct Cost: ¥21,100,000)
Fiscal Year 1990: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1989: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1988: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsProtease / calpain / cathepsin / proteasome / gene expression / アテプシン / 病態 / プロテアーゼ / プロテアーゼインヒビター / カルシウムプロテアーゼ / ATPプロテアーゼ / プロセシング
Research Abstract

1. Calcium-dependent protease
Functional analysis of the 5'-upstream region of the human calpain large subunit gene revealed that the presence of a functional TRE sequence. The results of the analyses of expression of the calpain gene indicated that the level of m-calpain is changed by various stimuli whereas that of mu-calpain stays constant. mu-calpain presumably plays house-keeping functions while mcalpain functions in signal response.
2. Lysosomal proteases
The gene structures of cathepsins H and L were determined and their gene expression was examined. The expression of these proteases was induced by both cAMP and TPA. significant amount of cathepsin L is secreted from cancer cells into medium, suggesting its functional importance in metastasis.
3. Multicatalytic proteinase (Proteasome)
cDNA cloning of subunits of proteasome from human, rat and yeast has been performed. Although more than 10 subunits have been cloned, none of them shows sequence similarity to other known proteases. Among 3 yeast subunits thus far cloned, one is not essential for growth, although the other two are indispensable. Gene disruption experiments are now in progress to clarify the function of the non-essential subunit in the proteasome function.

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] K.Suzuki: "Calciumーactivated neutral proteaseーーーstructureーfunctureーfunction relationーship and functional implications" Cell Structure Function. 15. 1-6 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Y.Nishimura: "Intracellular processing and actitvation of lysosomal cathepsins" Acta Histochem.Cytochem.23. 53-54 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] D.Muno: "Effect of metabolic alterations on dietary and the content of cathepsins B,H and L" Eur.J.Biochem.191. 91-98 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S.Ishiura: "Distribution of Alzheimer´s disease amyloid A4ーgenereating enzymes in rat brain tissues." Neurosci.Lett.115. 329-334 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H.Sorimachi: "Molecular cloning of cDNA for two subunits of rat multicatalytic protetinase" Eur.J.Biochem.193. 775-781 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T.Fujiwara: "Proteasomens are essential for yeast proliferation" J.Biol.Chem.265. 16604-16613 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] R.Mellgren: "CRC Press" Intracellular proteolytic system of animal cells, 288 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, K.: "Calcium-activated neutral protease ---- Structrural and functional implications." Cell Structure Function. 15. 1-6, (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nishimura, Y.: "Intracellular processing and activation of lysosomal cathepsins." Acta Histochem. Cytochem. 23. 53-64 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Muno, D.: "Effect of metabolic alterations on the dietary content of cathepsins B, L, and H." Eur. J. Biochem.191. 91-98 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ishiura, S.: "Distribution of Alzheimer's disease amyloid A4-generating enzymes in rat brain tissues" Neurosci. Letters,. 115. 329-334 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Sorimachi, H.: "Molecular cloning of cDNAs for two subunits of rat multicatalytic proteinases." Eur. J. Biochem.193. 775-781 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fujiwara, T.: "Proteasomes are essential for yeast proliferation." J. Biol. Chem.265. 16604-16613 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mellgren, R.: CRC Press. Intracellular proteolytic system of animal cells., 228 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] K.Suzuki: "Calciumーactivated neutral proteaseーーーーstructureーfunction relationship and functional implications" Cell Structure Function. 15. 1-6 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Nishimura: "Intracellular processing and activation of lysosomal cathepsins" Acta Histochem.Cytochem.23. 53-64 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] D.Muno: "Effect of metabolic alterations on the dietary and the content of cathepsins B,H and L" Eur.J.Biochem.191. 91-98 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Ishiura: "Distribution of Alzheimer's disease amyloid A4ーgenerating enzymes in rat brain tissues." Neurosci.Lett.115. 329-334 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Sorimachi: "Molecular cloning of cDNA for two subunits of rat multicatalytic proteinase" Eur.J.Biochem.193. 775-781 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Fujiwara: "Proteasomes are essential for yeast proliferation" J.Biol.Chem.265. 16604-16613 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] R.Mellgren: "Intracellular proteolytic system of animal cells" CRC Press, 288 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Nakamura: "Frangmentation of an endogenous inhibitor upon complex formation with high and low calcium-requiring forms of calcum-activated neutral protease" Biochemistry. 28. 449-455 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Kawasaki: "Identification and characterization of inhibitor sequence in four repeating domains of the endogenous inhibitor of calcium dependent protease" J.Biochemistry. 106. 274-281 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.Hata: "Tandemly reiterated negative enhancer-like sequence regulates transcription of a human gene for the large subunit of calcium dependent protease" J.Biol.Chem.264. 6404-6411 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Ishidoh: "Gene structure of cathepsin H" FEBS Letters.253. 103-107 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Fujiwara: "Molecular cloning of cDNA for proteasomes(Multicatalytic protease complex)from rat liver:Primary structure of the largest subunit" Biochemistry. 28. 7332-7340 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Tanaka: "Direct evidence for nuclear and cytoplasmic colocalization of proteasomes(multicatalytic protease complex)in liver" J.Cellular Physiology. 139. 34-41 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] W.Matthews: "Involvement of the proteasome in various degradative processes in mammalian cells" Proc.Natl.Acad.Sci.,USA. 86. 2597-2601 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Murachi: "Intracellular regulatory system involving calpain and calpastatin" Biochemistry International. 18. 263-294 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Tsukahara: "RNA degrading activity is tightly associated with the multicatalytic proteinase ingensin" FEBS Letters. 255. 179-183 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Ishiura: "Addition of ATP increases the apparent molecular mass of the multicatalytic proteinase,ingensin" FEBS Letters. 257. 123-126 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Ishiura: "Putative N-terminal splitting enzyme of amyloid A4 peptride is the multicatalytic proteinase,ingensin,widely distirbuted among mamalin cells" FEBS Letters. 257. 388-392 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Ishiura: "Identification of a putative amyloid A4 generating enzyme as a prolyl endopeptidase" FEBS Letters. 260. 131-134 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Takahashi: "Purification and characterization of porcine proline-beta-naphthl amidase,a novel enzyme from intestinal mucosa" J.Biol.Chem.264. 11565-11571 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Yanagisawa: "Myelin-associated calpain II" J.Neurochem.51. 803-807 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Mizuno: "A unique membrane-bound,calcium dependent endopeptidase with specificity toward paired basic residues in rat liverGolgi Fraction" Biochem.Biophys.Res Commun.164. 780-787 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] J.Hino: "Isolation and identification of human brain natriuretic peptides in human cardiac atrium" Biochem.Biophys.Res.Commun.

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Maki: "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene" J.Biol.Chem.264. 18866-18869 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Murachi,T.: "The calpain-calpastatin system in hepatic cells" Calcium Protein Signaling(Hidaka,H.Ed.,Plenum Press). 445-454 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] N.Katunuma: "Possible regulatory mechanisms of intracellular protein catabolism through lysosome" Intracellular Proteolysis(Japan Sci.Soc.Press,Tokyo)(Katunuma,N.,Kominami,E.eds). 3-23 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ishodoh,K.: "Gene structure of rat cathepsin L" FEBS Letters. 252. 103-107 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Niwa: "Studies on the reactive site of the cystatin super family using recombinatnt cystatin A mutant.QVVAG is not essential" FEBS Lettrs. 255. 309-314 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Nishimura: "Evidence that aspartic protease is inbolved in the proteolytic processing event of rat procathepsin L in lysosomes" Arch.Biochen.Biophys.271. 400-406 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Nishimura: "Intracellular processing and activation of lysosomal cathepsin L" Intracellular Proteolysis(N.Ktunuma and E.Kominami,eds.,Jpn Sci.Soc.Press,Tokyo). 61-73 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Suzuki.;S.Imajoh.;Y.Emori.;H.Kawasaki.;Y.Minami.;S.Ohno.: Adv.Enzyme Regul.28. 153-169 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] K.Tanaka.;T.Yoshimura.;A.Ichihara.;A.Ikai.;A.Nigai.;Y.Morimoto.;M.Sato.;N.Tanaka.;Y.Katsube.: J.Mol.Biol.203. 985-996 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Nishimura.;K.Furuno.;K.Kato.: Arch.Biochem.Biophys.263. 107-116 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Tsukahara.;S.Ishiura.;H.Sugita.: Proc.Japan Acad.64,Ser.B. 72-75 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] S.Yoshikawa.;T.Tashiro.;K.Takahashi.: J.Biochem.104. 1007-1010 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Tsujinaka.;Y.Kajiware.;J.Kanbayashi.;J.Sakon.;M.Higuchi.;T.Tanaka.;T.Mori.: Biochem.Biophys.Res.Commun.153. 1201-1208 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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