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Functions of the Maf transcription factors in development and differentiation

Research Project

Project/Area Number 16590215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SAKAI Masaharu  Hokkaido University, School of Medicine, Professor, 医学部, 教授 (50162269)

Co-Investigator(Kenkyū-buntansha) IMAKI Junko  National Defense Medical College, Professor, 教授 (20223323)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsChondrocyte / Cellular differentiation / Transcription factors / Maf / CTGF / GST-P / C / EBP / DNA micro-array / 標的遺伝子 / ノックアウトマウス
Research Abstract

1,c-Maf regulates CTGF gene ; We have previously reported that the c-Maf and MafB transcription factors were specifically expressed in the differentiation process of lens, cartilage, spinal cord and kidney. However the target genes and functions in these tissues are not known. Introduction of the Maf gene into the fibroblast cell line using adenovirus vector induced connective tissue growth factor (CTGF) gene, which has pivotal functions in cartilage development. From the detailed analyses, including EMSA, reporter transfection and ChIP analyses, c-Maf binds to the promoter region and 5'-untranslated regions of CTGF gene and strongly activates this gene. (Biochem Biophys Res Commn 339,1089-1097,2006)
2.Identification of c-Maf target genes by DNA micro-array analysis : To identify the target genes of c-Maf, we have performed DNA micro-array analysis using the mouse embryonic fibroblast (MEF) cells from wild and c-maf knock-out mice. We identified several genes, including fibroblast growth factors (Fgf 18 and Fgf 9), which significantly reduced the expression in KO-MEF cells. The detailed analyses on these genes are currently in progress.
3,Regulation of glutathione S-transferase (GST-P) gene during hepatocarcinogenesis. GST-P is a tumor marker activated by the Nrf2/MafK hetero-dimers in early stage of carcinogenesis (Biochemical J.380,515-521,2004). Recently, we identified the CAAT enhancer binding protein α (C/EBPα) as a suppressor of this gene in the normal liver. C/EBPα specifically binds to the GPE1,a strong enhancer element of GST-P gene, in vitro and in vivo. C/EBPα expressed in normal liver and strongly inhibited the Nrf2/MafK activity by competing the binding site (GPE1) with the Nrf2/MafK. In the early stage of carcinogenesis, the C/EBPα expression is completely shut-off, and the substitution of GPE1 binding factor from C/EBPα to the Nrf2/MafK lead to the strong induction of GST-P expression. (J.Biol.Chem.in press)

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (28 results)

All 2006 2005 2004 Other

All Journal Article (27 results) Book (1 results)

  • [Journal Article] Activation of Connective Tissue Growth Factor Gene by the c-Maf and Lc-Maf Transcription Factors.2006

    • Author(s)
      Omoteyama K. et al.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 1089-1097

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CCAAT enhancer binding protein α(C/EBP α) suppresses the rat placental glutathione S-transferase gene in normal liver.2006

    • Author(s)
      Ikeda, H. et al.
    • Journal Title

      J. Biol. Chem. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice.2006

    • Author(s)
      Kase S.et al.
    • Journal Title

      Acta Histochem 107

      Pages: 469-472

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of Connective Tissue Growth Factor Gene by the c-Maf and Lc-Maf Transcription Factors2006

    • Author(s)
      Omoteyama K. et al.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 1089-1097

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CCAAT enhancer binding protein α (C/EBP α) suppresses the rat placental glutathione S-transferase gene in normal liver.2006

    • Author(s)
      Ikeda, H. et al.
    • Journal Title

      J Biol.Chem. (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interleukin-6 and Mevastatin Regulate Plaminogen Activator Inhibitor-1 Through CCAAT/Enhancer-Binding Protein-δ.2005

    • Author(s)
      Dong, J. et al.
    • Journal Title

      Arterioscler Thrormb Vasc Biology 25

      Pages: 1078-1084

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice.2005

    • Author(s)
      Kase S.et al.
    • Journal Title

      Acta Histochem. 107

      Pages: 469-472

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Regulation of GST-P gene expression during hepatocarcinogenesis.2005

    • Author(s)
      Sakai.M.et al.
    • Journal Title

      Methods in Enzymology (Elsevier) vol. 401

      Pages: 20-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of GST-P gene expression during hepatocarcinogenesis.2005

    • Author(s)
      Sakai M., et al.
    • Journal Title

      Methods in Enz. 401

      Pages: 42-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interleukin-6 and Mevastatin Regulate Plaminogen Activator Inhibitor-1 Through CCAAT/Enhancer-Binding Protein-δ.2005

    • Author(s)
      Dong J.et al.
    • Journal Title

      Arterioscler Thrormb Vasc Biol. 25

      Pages: 1078-1084

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of GST-P gene expression during hepatocarcinogenesis2005

    • Author(s)
      Sakai, M., Muramatsu, M
    • Journal Title

      Methods in Enz. 389(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of c-maf and mafB genes in the skin during rat embryonic development.2004

    • Author(s)
      Ogata A. et al.
    • Journal Title

      Acta histochemica 106

      Pages: 65-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis.2004

    • Author(s)
      Ikeda, H. et al.
    • Journal Title

      Biochemical J 380

      Pages: 515-521

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional mapping of tissue-specific elements of the human alpha-fetoprotein gene enhancer.2004

    • Author(s)
      Nakabayashi, H. et al.
    • Journal Title

      Biochem Biophys Res Commun 318

      Pages: 773-785

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Developmental contribution of c-maf in the kidney : distribution and developmental study of c-maf mRNA in normal mice kidney and histological study of c-maf knock out mice kidney and liver.2004

    • Author(s)
      Imaki J. et al.
    • Journal Title

      Biochem Biophys Res Commun., 320

      Pages: 1323-1327

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of maf-B mRNA in the epithelium around the eyelid closure of the mouse eye at embryonic day 18.2004

    • Author(s)
      Kase S.et al.
    • Journal Title

      Anat Embryol 209・2

      Pages: 153-156

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of c-maf and mafB genes in the skin during rat embryonic development.2004

    • Author(s)
      Ogata, A. et al.
    • Journal Title

      Acta histochemica. 106

      Pages: 65-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis.2004

    • Author(s)
      Ikeda, H. et al.
    • Journal Title

      Biochemical J. 380

      Pages: 515-521

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional mapping of tissue-specific elements of the human alpha-fetoprotein gene enhancer.2004

    • Author(s)
      Nakabayashi H, et al.
    • Journal Title

      Biochem Biophys Res Commun. 318

      Pages: 773-785

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Developmental contribution of c-maf in the kidney : distribution and developmental study of c-maf mRNA in normal mice kidney and histological study of c-maf knockout mice kidney and liver.2004

    • Author(s)
      Imaki J, et al.
    • Journal Title

      Biochem Biophys Res Commun 320

      Pages: 1323-1327

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of maf-B mRNA in the epithelium around the eyelid closure of the mouse eye at embryonic day 18.2004

    • Author(s)
      Kase S, et al.
    • Journal Title

      Anat Embryol (Berl). 209

      Pages: 153-156

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of c-maf and mafB genes in the skin during rat embryonic development2004

    • Author(s)
      Ogata A, Shimizu T, Abe R, Shimizu H, Sakai M.
    • Journal Title

      Acta histochemica 106

      Pages: 65-67

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis2004

    • Author(s)
      Ikeda, H., Nishi, S., Sakai, M.
    • Journal Title

      Biochemical J 380

      Pages: 515-521

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional mapping of tissue-specific elements of the human alpha-fetoprotein gene enhancer.2004

    • Author(s)
      Nakabayashi H, Koyama Y, Suzuki H, Li HM, Sakai M, Miura Y, Wong NC, Niahi S
    • Journal Title

      Biochem Biophys Res Commun 318

      Pages: 773-785

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Developmental contribution of c-maf in the kidney : distribution and developmental study of c-maf mRNA in normal mice kidney and histological study of c-maf knock out mice kidney and liver2004

    • Author(s)
      Imaki J, Tsuchiya K, Mishima T, Onodera H, Kim JI, Yoshida K, Ikeda H, Sakai M
    • Journal Title

      Biochem Biophys Res Commnun. 320

      Pages: 1323-1327

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expreasion of maf-B mRNA in the epithelium around the eyelid closure of the mouse eye at embryonic day 182004

    • Author(s)
      Kase S, Imaki J, Harada T, Harada C, Ohgami K, Shiratori K, Sakai M, Nishi S, Ohno S. Yoshida K
    • Journal Title

      Anat Embryol 209・2

      Pages: 153-156

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CCAAT enhancer binding protein α (C/EBP α) suppresses the rat placental glutathione S-transferase gene in normal liver.

    • Author(s)
      Ikeda H. et al.
    • Journal Title

      J.Biol.Chem. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Methods in Enzymology vol.4012005

    • Author(s)
      Sakai M. et al.
    • Total Pages
      20
    • Publisher
      Elsevier
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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