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Molecular mechanisms of pigment cell differentiation.

Research Project

Project/Area Number 08457043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

SHIBAHARA Shigeki  Tohoku University School of Medicine, Professor, 医学部, 教授 (70206142)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Kazuhiro  Tohoku University School of Medicine, Lecturer, 医学部, 講師 (80241628)
YASUMOTO Ken-ichi  Tohoku University School of Medicine, Assistant Professor, 医学部, 助手 (90241629)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordsmelanin / tyosinase / TRP-1 / TRP-2 / transcription factor / microphthalmia / TRF-1 / TRF-2
Research Abstract

Microphthalmia-associated transcription factor (MITF) plays an important role in pigment cell differentiation. Transient transfection assays have shown that MITF transactivates the tyrosinase and tyrosinase-related protein 1 (TRP-1) gene promoters, but not the TRP-2 gene promoter. Unexpectedly, a truncated MITF lacking the carboxyl-terminal 125 amino acids could transactivate the TRP-2 promoter. Consequently, using a yeast two-hybrid system, we have cloned several cDNAs coding for proteins which may interact with MITF's carboxyl-terminal portion. Moreover, we have identified three novel MITF isoforms, termed A,B,and H types, which differ in their amino-termini and expression patterns. An authentic MITF has been renamed MITF-M,because it is exclusively expressed in melanocytes and melanoma. These four isoforms share the entire carboxyl-terminal portion, including a basic helix-loop-helix and leucine zipper structure. We have shown that MITF-A,like MITF-M,transactivates the tyrosinase and TRP-1 gene promoters, but not-TRP-2. MITF-A mRNA is predominantly expressed in retinal pigment epithelium. In addition, we have obtained the following results as summarized below. 1.The threc cis-regulatory elements of the human tyrosinase gene have been identified, and each of these elements contains one copy of a CATGTG motif and is required for pigment cell-specific transcription. 2.A human TFEC isoform, termed TFECL,has been identified as a transcriptional activator. TFECL contains an activation domain which is deleted in rat TFEC,originally identified as a transcriptional repressor in rat chondrosarcoma. 3.The amino acid sequence of rat neurofibromin has been deduced from the nucleotide sequence of its cDNA.4.Adrenomedullin, a potent vasodilator peptide, has been shown to be produced and secreted by cultured choroid plexus carcinoma cells, a rare neoplasm derived from the epithelium of the choroid plexus.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Nakayama, M.: "Induction of Adrenomedullin by Hypoxia and Cobalt Chloride in Human Colorectal Carcinoma Cells." Biochem.Biophys.Res.Commun.印刷中 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K.: "Production and Secretion of Adrenomedullin from Glial Cell Tumors and its Effects on cAMP Production." Peptides. 18. 1117-1124 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K.: "Expression of Adrenomedullin mPNA in the Human Brain and Pituitary." Peptides. 18. 1051-1053 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasumoto, K.: "Molecular Cloning of a cDNA Encoding a Human TFEC Isoform,a Newly Identified Transcriptional Regulator." Biochim.Biophys.Acta. 1353. 23-31 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K.: "Possible Implications of the Induction of Human Heme Oxygenase-1 by Nitric Oxide Donors." J.Biochem.(Tokyo). 121. 1162-1168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimpara, T.: "Microsatellite Polymorphism in the Human Heme Oxygenase-1 Gene Promoter and its Application in Association Studies with Alzheimer and Parkinson Disease." Hum.Genet. 100. 145-147 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K.: "Production and Secretion of Adrenomedullin by Cultured Choroid Plexus Carcinoma Cells" J.Neurochem.68. 726-731 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasumoto, K.: "Functional Analysis of Microphthalmia-Associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes." J.Biol.Chem.272. 503-509 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki, H.: "Differential Tissue-Specific Expression of Neurofibromin Isoform mRNAs in Rat." J.Biochem.(Tokyo). 120. 1048-1054 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibahara, S.: "The Pigmentary System.Physiology and Pathophysiology" Oxford University Press 印刷中, (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakayama, M., Takahashi, K., Murakami, O., Shirato, K., and Shibahara, S.: "Induction of Adrenomedullin by Hypoxia and Cobalt Chloride in Human Colorectal Carcinoma Cells." Biochem.Biophys.Res.Commun.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K., Satoh, F., Hara, E., Sone, M., Murakami, O., Kayama, T., Yoshimoto, T.and Shibahara, S.: "Production and Secretion of Adrenomedullin from Glial Cell Tumors and its Effects on cAMP Production." Peptides. 18. 1117-1124 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K., Satoh, F., Sone, M., Murakami, O., Sasano, H., Mouri, T.and Shibahara, S.: "Expression of Adrenomedullin mRNA in the Human Brain and Pituitary." Peptides. 18. 1051-1053 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yasunoto, K.and Shibahara, S.: "Molecular Cloning of a cDNA Encoding a Human TFEC Isoform, a Newly Identified Transcriptional Regulator." Biochim Biophys.Acta. 1353. 23-31 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K., Hara, E., Ogawa, K., Kimura, D., Fujita, H.and Shibahara, S.: "Possible Implications of the Induction of Human Heme Oxygenase-1 by Nitric Oxide Donors." J.Biochem. (Tokyo). 121. 1162-1168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] da Silva, J.-L., Stoltz, R.A., Dunn, M.W., Abraham, N.G.and Shibahara, S.: "Diminished Heme Oxygenase-1 mRNA Expression in RPE Cells from Diabetic Donors as Quantitated by Competitive RT/PCR." Curr.Eye Res.16. 380-386 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimpara, T., Takeda, A., Watanabe, K., Itoyama, Y., Ikawa, S., Watanabe, M., Arai, H., Sasaki, H., Higuchi, S., Okita, N., Takase, S., Saito, H., Takahashi, K.and Shibahara, S.: "Microsatellite Polymorphism in the Human Heme Oxygenase-1 Gene Promoter and its Application in Association Studies with Alzheimer and Parkinson Disease." Hum.Genet.100. 145-147 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, K., Satoh, F., Hara, E., Murakami, O., Kumabe, T., Tominaga, T., Kayama, T., Yoshimoto, T.and Shibahara, S.: "Production and Secretion of Adrenomedullin by Cultured Choroid Plexus Carcinoma Cells." J.Ncurochem. 68. 726-731 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamamoto, K., Yokoyama, K., Takahashi, K., Tomita, Y.and Shibahara, S.: "Functional Analysis of Microphthalmia-Associated Transcription Factor in Pigment Cell-specfic Transcription of the Human Tyrosinase Family Genes." J.Biol.Chem.272. 503-509 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suzuki, H., Takahashi, K., Yasumoto, K., Fuse, N.and Shibahara, S.: "Differential Tissue-Sppecific Expression of Neurofibromin Isoform mRNAs in Rat." J.Biochem. (Tokyo). 120. 1048-1054 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibahara, S., Yasumoto K.and Takahashi, K.: Genetic Regulation of the Pigment Cell. In The Pigmentary System. Physiology and Pathophysiology, edited by J.J.Nordlund, R.E.Boissy, V.J.Hearing, R.A.King and J.-P.Ortonne. (in press). Oxford University Press, New York, NY,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakayama, M.: "Induction of Adrenomedllin by Hypoxia and Cobalt Chloride in Human Colorcctal Carcinoma Cells." Biochem.Biophys.Res.Commun.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi, K.: "Production and Secretion of Adrenomedullin from Glial Cell Tumors and its Effects on cAMP Production." Peptides. 18. 1117-1124 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi, K.: "Exprcssion of Adrenomedullin mRNA in the Human Brain and Pituitary." Pcptidcs. 18. 1051-1053 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasumoto, K.: "Molecular Cloning of a cDNA Encoding a Human TFEC Isoform,a Newly Identified Transcriptional Regulator." Biochim.Biophys.Acta. 1353. 23-31 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi, K.: "Possiblc Implications of Induction of Human Heme Oxygenasc-1 by Nitric Oxide Donors." J.Biochem.(Tokyo). 121. 1162-1168 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kimpara, T.: "Micosatellite Polymorhism in the Human Heme Oxygenase-1 Gene Promoter and its Application in Association Studies with Alzheimer and Parkinson Disease." Hum.Genet.100. 145-147 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shibahara, S.: "The Pigmcntary System.Physiology and Pathophysiology" Oxford Univcrsity Prcss(印刷中), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasumoto K. & Shibahara S.: "Molecular Cloning of a cDNA Encoding a Human TFEC Isofrom, a Newly Identified Transcriptional Regulator." Biochim. Biophys. Acta. 印刷中. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasumoto K. et al.: "Functional Analysis of Microphthalmia-Associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes." J. Biol. Chem.272. 503-509 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahashi K. et al.: "Production and Secretion of Adrenomedullin by Cultured Choroid Plexus Carcinoma Cells." J. Neurochem.68. 726-731 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki H. et al.: "Differential Tissue-Specific Expression of Neurofibromin Isofrom mRNAs in Rat." J. Biochem. (Tokyo). 120. 1048-1054 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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