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Physiological function of proprotein convertase PACE4

Research Project

Project/Area Number 09670129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

MATSUDA Yoshiko  The University of Tokushima, Faculty of Engineering Professor, 工学部, 教授 (40035449)

Co-Investigator(Kenkyū-buntansha) NAGAHAMA Masami  Tokyo University of Pharmacy and Life Science School of Life Science Research As, 生命科学部, 助手 (60281169)
TSUJI Akihiko  The University of Tokushima, Faculty of Engineering Assistant Professor, 工学部, 助教授 (20155360)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsPACE4 (SPC4) / proprotein convertase / processing protease / SPC family / bHLH transcription / serum albumin / neurogenesis / 補体C3プロセシング / PACE4(SPC4) / 前駆性タンパク質プロセシング / 血清アルプミンプロセシング / Kexin様プロテアーゼ / 生理活性ペプチドプロセシング
Research Abstract

PACE4 (paired basic amino acid cleaving enzyme) is a member of a family of the mammalian kexin-like proprotein convertases containing a subtilisin-like catalytic domain. To determine the origin of these isoforms, the entire human PACE4 gene Las been isolated as a set of overlapping genomic DNA fragments, and analyzed by restriction enzyme digestion and nucleotide sequence determination. The human PACE4 gene spans at least 250 kb and is distributed over 25 exons that range in e from 39 to 1,422 base pairs. Human PACE4 gene is the largest kexin-like proprotein convertase gene reported to date. The most striking feature of its genomic structure is the size of the introns and the number of exons, although the general organization of signal peptide, propeptide, and catalytic domains, which are conserved in this family, is very similar to that reported for other kexin-like protease genes. The structural analysis of PACE4 genomic DNA indicates that multiple PACE4 transcripts are produced as a consequence of alternative RNA splicing events, including exon skipping, and differences in the usage of the inner 5'-splicing donor and polyadenylation sites. A major transcriptional start site was detected 314 bp upstream from the ATG translational start site by primer extension analysis. Sequence analysis of the 5'-flanking region revealed that PACE4 gene lacks TATA and CCAAT boxes in the proximal upstream region of the start site, although potential binding sites for several transcription factors including SP1, AP1, AP2, PEA3, Ets-1, GHF(growth hormone factor)-1, CREB(cyclic AMP response element binding protein), and basic helix-loop-helix proteins, were present. An unusual sequence of six tandem repeats of a nonadecamer (GGCCTGGGGGTTCACCTGC) containing an E box is found in the 5-flanking region. These results suggest that PACE4 is not a constitutive gene product and its expression is regulated by various transcription factors.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Mori,K.et al.: "Subtilisin-Like Proprotein Convertases,PACE4 and PC7/8,as well as Furin,are Endogeneous Proalbumin Convertases in HepG2 Cells" Journal of Biochemistry. 125. 627-633 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahama,M.et al.: "Proteolytic Cleavage of the Neural Cell Adhesicn Molecule L1 by Subtilisin-Like Proprotein Convertase" Neural Development. 261-266 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahama,M.et al.: "Biosynthetic Processing and Quantermary Interaction of Proprotein Convertase SPC4C (PACE4)" FEBS Letter. 43・4. 155-159 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akamatsu,T.et al.: "Developmental Expression of a Novel kexin Family protease,PACE4E in the Rat Olfactory System" Histochem.Cell Biol.108. 95-103 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori,K.et al.: "A Novel Human PACE4 isoforms,PACE4E Is an Active Processing Protease Containing a Hydrophobic Cluster at the Carboxy Terminus" Journal of Biochemistry. 121. 941-948 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji,A.et al.: "Genomic Organization and Alternative Splicing of Human PACE4 (SPC4),Kexin-like Processing Endoprotease" Journal of Biochemistry. 122. 438-452 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagamune,H.et al.: "Cyclic AMP-Inducible procalcitonin Processing in Thyroidal Parafollicular Cells is Requlated by the Kexin Family Protease,PC1" Medical Aspect of Proteases and Protease Inhibitors,IOS Press,Amsterdam. 22-33 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori, K., Tsuji, A., Matsuda, Y.et al.: "Subtlisin-like Proprotein Convertase, PACE4 and PC7/8 as well as Furin are Endogenesis Proalbumin Convertase in HepG2 Cells" J.Biochem.125. 627-633 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahama, M., Tsuji, A., Matsuda, Y.et al.: "Proteolysic Cleavage of the Neural Cell Adhesicn Molecule L_1 by Subtilisin-Like Proprotein convertase" Neural Development. 261-266 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagahama, M., Tsuji, A., Matsuda, Y.et al.: "Biosynthetic processing and quateruary interactions of proprotein convertase SPC4 (PACE4)" FEBS Lett.434. 155-159 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akamatsu, T., Nagamune, H., Tsuji, A., Matsuda, Y.et al.: "Developmental Expression of a Novel kexin Fami1y protease, PACE4E in the Rat Olfactory System" Histochem.Cell Biol.108. 95-103 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori, K., Kii, S., Tsuji, A., Matsuda, Y.et al.: "A Novel Human PACE4 isoforms, PACE4E Is an Active Processing Protease Containing a Hydrophobic Cluster at the Carboxy Terminus" J.Biochem.121. 941-948 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji, A., Hine, C., Matsuda, Y.et al.: "Genomic Organization and Alternative Splicing of Human PACE4 (SPC4), Kexin-like Processing Endoprotease" J.Biochem.122. 438-452 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagamune, H., Tsuji, A., Matsuda, Y.et al.: "Cyclic AMP-Inducible procalcitonin Processing in Thyroidal Parafollicular Cells is Regulated by the Kexin Family Protease, PC1" Medical Aspect of Proteases and Protease Inhibitors, IOS Press Amsterdam. 22-33 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 森 健二 他: "先天性異常アルブミン症、無アルブミン血症、先天代謝異常症候群-遺伝子解析の進歩と成果-(下巻)" 日本臨床. 19. 657-660 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagahama,M.,et al.: "Proteolysic Cleavage of the Neural Cell Adhesisn Molecule bySubtilisin-Like proprotein Convertase" Neural Development. 261-266 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagahama,M.,et al.: "Biosynthetic Processing and Quantemary interactions of Proprotein ConvertaseSPC4C(PACE4)" FEBSLetter. 434. 155-159 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,K.,et al.: "Subtilisin-like proprotein Convertases,PACE4 and PC7/8,as well as Furin,are Endogeneous Proalbumin Convertases in HepG2cells" Joumal of Biochemistry. 125. 627-633 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Mori, Y.Matsuda, et al.: "A Novel Human PACE4 Isoform,PACE4E Is an Active Processing Protease Containing a Hydrophobic Cluster at the Carboxy Terminus" J.Biochem(Tokyo). 121. 941-948 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Akamatsu, Y.Matsuda, et al.: "Developmental Expression of a Novel Kexin Family Protease,PACE4E,in the Rat Olfactory System" Histochem.Cell Biol. 108. 95-103 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Tsuji, Y.Matsuda, et al.: "Genomic Organization and Alternative Splicing of Human PACE4(SPC4),Kexin-Like Processing Endoprotease" J.Biochem(Tokyo). 122. 438-452 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Nagamune, Y.Matsuda, et al.: "Cyclic AMP-inducible Procalcitonin Processing in Thyroidal Parafollicular Cells is Regulated by the Kexin-family Protease,PC1" Medical Aspects of Proteases and Protease Inhibitors IOS Press,Amsterdam. 22-23 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松田 佳子, 辻明彦: "前駆体蛋白質の活性化とケキシンファミリー,プロセシングプロテアーゼ" 蛋白質核酸酵素. 42. 2355-2361 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Tsuji, Y.Matsuda, et al.: "Gene Organization and Alternative Splicing of Human PACE4,Subtilisin-like Proprotein Convertase" FASEB.J.11. A1224 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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