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MOLECULAR BIOLOGY FOR SYNTHESIS OF GIANT PIGMENT GRANULES IN CONGENITAR PIGMENTARY DISEASES

Research Project

Project/Area Number 12470179
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionSapporo Medical University

Principal Investigator

JIMBOW Kowichi  Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (30094238)

Co-Investigator(Kenkyū-buntansha) MATSUSAKA Hidenobu  Sapporo Medical University, School of Medicine, Assistant, 医学部, 助手 (20311889)
ONO Ichiro  Sapporo Medical University, School of Medicine, Lecture, 医学部, 講師 (20125298)
YAMASHITA Toshiharu  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (50167706)
南辻 泰志  札幌医科大学, 医学部, 助手 (00305236)
大森 房之  札幌医科大学, 医学部, 講師 (00315524)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
Keywordsmelanosome / tyrosinase / calnexin / giant granules / pigmentation / melanin / メラニン生合成 / 分子シャペロン / 小胞輸送 / チロジナーゼ
Research Abstract

This study examines the target signals for the vesicular transport of tyrosinase and its related proteins (TRP-1,2) from Golgi (TGN) to melanosomes, in the hope to identify the biological and molecular mechanism involved in the synthesis of giant pigment granules in congenital pigmentary diseases. Specifically this study focused on characterization of the biological role of a low molecular weight GTP-binding protein, Rab7. To investigate the requirement of Rab7-containing compartments for vesicular transport of tyrosinase family proteins, we expressed tyrosinase and TRPs by recombinant adenovirus and analyzed their localization in human amelanotic melanoma cells in the presence or absence of a dominant-negative mutant of Rab7 (Rab7N125I). Co-infection (Ad-HT) and TRP-1 (Ad-TRP-1) resulted in the enhancement of tyrosinase activity and melanin production compared to a single infection of Ad-HT. In the Ad-HT-infected cells many of the newly synthesized tyrosinase proteins were colocalized in lysosomal Igp85-positive granules of the entire cytoplasm, whereas in the presence of Rab7N125I the colocalization tyrosinase and Igp85 proteins was decreased markedly in the distal area of the cytoplasm. In the Ad-TRP-1-infected cells, TRP-1 was detected throughout the cytoplasm, but not colocalized in prelysosomal (early endosomal) EEA-1 granules. In the presence of Rab7N125I, however, TRP-1 was retained in the EEA-1-positive granules.
We are in the process of analyzing the functional domains of TRP-1 and tyrosinase in this vesicular transport of the melanosome biosynthesis.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Sahara H et al.: "A gene encoding human gastric signet ring cell carcinoma antigen recognized by HLa-A31-restricted cytotoxic T lymphocytes"J Immunotherapy. 25・3. 235-242 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto Y et al.: "An immunosuppressive effect by synthetic sulfonolipids deduced from sulfonoquinovosly diachlglycerols of sea urchin"Transplantation. 74・2. 261-267 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirosaki K et al.: "Tyrosinase and tyrosinase related protein-1 (TRP-1) require Rab-7 for their intracellular transport"J Invest Dermatol.. 119. 475-480 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki Y et al.: "The p53 family member genes are involved in the notch signal pathway"J Biol Chem.. 277. 719-724 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] King KE et al.: "DelNp63 functions as a positive and negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes"Oncogene.. (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] Takahashi M et al.: "E1B-55K-Deleted Adenovirus Expressing E1A-13S by AFP-Enhancer/Promoter Is Capable of Highly Specific Replication in AFP-Producing Hepatocellular Carcinoma and Eradication of Established Tumor"Mol Ther.. 5. 627-634 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sahara H et al.: "A gene encoding human gastric signet rings cell carcinoma antigen recognized by HL1-A31-restricted cytotoxic T lymphocytes"J Immunotherapy. 25・3. 235-242 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto Y et al.: "An immunosuppressive effect by synthetic sulfonolipids deduced from sulfonoquinovosly diacylglycerols of sea urchin"Transplantation. 74・2. 261-267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirosaki K et al.: "Tyrosinase and tyrosinase related protein-1 (TRP-1) require Rab-7 for their intracellular transport"J Invest Dermatol. 119. 475-480 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki Y et al.: "The p53 family member genes are involved in the notch signal pathway"J Biol Chem. 277. 719-724 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M et al.: "E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor"Mol Ther. 5. 627-634 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] King KE et al.: "DelNp63 functions as a positive and negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes"Oncogene. (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] Sahara H et al.: "A gene encoding human gastric signet ring cell carcinoma antigen recognized by HLa-A3 1-restricted cytotoxic T lymphocytes"J Immunotherapy. 25・3. 235-242 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsumoto Y et al.: "An immunosuppressive effect by synthetic sulfonolipids deduced from sulfonoquinovosly diacyiglycerols of sea urchin"Transplantation. 74・2. 261-267 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirosaki K et al.: "Tyrosinase and tyrosinase related protein-1 (TRP-1) require Rab-7 for their intracellular transport"J Invest Dermatol.. 119. 475-480 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sasaki Y et al.: "The p53 family member genes are involved in the notch signal pathway"J Biol Chem.. 277. 719-724 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] King KE et al.: "DelNp63 functions as a positive and negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes"Oncogene.. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi M et al.: "E1B-55K-deleted adenovirus expressing E1A-13S by APP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor"Mol Ther.. 5. 627-634 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jimbow Ket al.: "Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase related protein in vitiligo"Bri J Dermatol. 144. 55-65 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashita et al.: "Induction of apoptosis in melanoma cell lines by p53 and its related proteins"J Invest Dermatol. 117(4). 914-919 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gomez PF et al.: "Identification of rab 7 as a melanosome associated protein involved in the intracellular transport of tyrosinase related protein 1 (TRP-1)"J Invest Dermatol. 117(1). 81-90 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chen H et al.: "The role of phosphoinositide 3-kinase in the sorting and transport of newly synthesized tyrosinase-related protein-1 (TRP-1)"J Invest Dermatol Sym Proc. 6(1). 105-114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinoda K et al.: "A melanosome-associated monoclonal antibody J1 recognizes luminal membrane of Prelysosomes common to biogenesis of melanosomes and lysosornes"Cell Struct Fune. 26. 169-177 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokota S et al.: "Herpes simplex virus type 1 suppresses the interferon signaling pathway by inhibiting phosphorylation of STATs and janus kinases during an early infection stage"Virology. 286・1. 119-124 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoneta A,Yamashita T,Jin H-Y,Iwasaki A,Kondo A,Jimbow K: "Development of squamous cell carcinoma by two high-risk human papillomaviruses (HPVa), a novel HPV-67 and HPV-31 from bowenoid papulosis"British Journal of Dermatology. 143. 604-608 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jimbow K,Park JS,Kato F,Hirosaki K,Toyofuku K,Hua C,Yamashita T: "Assembly, target signal and intracellular transport of tyrosinase gene family protein in the initial stage of melanosome biogenesis"Pigment Cell Research. 13. 222-229 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jimbow K, et al.: "Intracellular vesicular trafficking of tyrosinase gene family protein in eu^- and pheomelanosome biogenesis"Pigment Cell Research. 13(Suppl.8). 110-117 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 神保孝一: "悪性黒色腫:メラニン代謝と標的化学療法の確立"組織培養工学. 26(10). 393-397 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 神保孝一: "色素細胞の生物学"日皮会誌. 110(12). 1940-1944 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gili A,Thomas PD,Ota M,Jimbow K: "Comparison of in vitro cytotoxicity of N-acetyl and N-propionyl derivatives for phenolic thioether amines in melanoma and neuroblastoma...."Melanoma Research. 10(1). 9-15 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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