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GDNF-inducible zinc finger protein 1 regulates organogenesis as a sequence specific transcriptional repressor

Research Project

Project/Area Number 16590309
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNagoya University

Principal Investigator

ICHIHARA Masatoshi  Nagoya University, School of Medicine, Associate Professor, 医学部, 助教授 (00314013)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Masahide  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40183446)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsRET / GDNF / GZF1 / ureteric bud / BTB / POZ / HOXA10
Research Abstract

By differential display analysis, we have recently identified a novel GDNF-inducible gene named GZF1 (GDNF-inducible zinc finger protein 1). GZF1 encodes a protein with a BTB/POZ domain at the N-terminus and 10 tandemly repeated C2H2 zinc finger motifs. The fact that antisense phosphorothioated oligodeoxynucleotides of the GZF1 gene markedly impair the ureteric bud branching in the metanephric organ culture suggests that GZF1 expression mediated by GDNF may play a role in renal branching morphogenesis. In this study, we first demonstrated the DNA binding property of GZF1 and its potential target gene. Using the cyclic amplification and selection of targets technique (CAST method), the consensus DNA sequence to which GZF1 binds was determined. Deletion mutants of GZF1 revealed that zinc fingers 1-6 of GZF1 are necessary for full DNA binding ability. Electrophoretic mobility shift assay revealed that GZF1 specifically binds to the determined consensus sequence and suppresses transcription of the luciferase gene from the HOXA10 gene regulatory element. Moreover, GZF1 target sequence was found in the 5' regulatory region of the HOXA10 gene that is a homeobox protein expressed during kidney development. Chromatin fragments containing GZF1 target sequence in HOXA10 promoter were specifically precipitated with anti-GZF1 antibody. These results demonstrated that GZF1 binds to the recognition sequence in the HOXA10 regulatory region in vivo (Morinaga T, Nucleic Acids Res. 2005). Next, we explored a GZF1 binding protein to further elucidate the molecular mechanism of GZF1. Using LC/MS/MS, we identified two known proteins immunoprecipitated with GZF1. We focused on one of these proteins. The endogenous protein was actually immunoprecipitated with GZF1 as well as the overexpressed one. Furthermore, this protein was co-localized with GZF1 in the cell nucleus. We have been now determining the GZF1-binding domain in this protein and a functional role in the kidney development.

Report

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

    (11 results)

All 2005 2004

All Journal Article (11 results)

  • [Journal Article] GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region2005

    • Author(s)
      Morinaga T
    • Journal Title

      Nucleic Acids Res 33

      Pages: 4191-4201

    • 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] Mi-3beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription2005

    • Author(s)
      Shimono K
    • Journal Title

      J Biol Chem 280

      Pages: 39436-39447

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Akt/PKB regulates actin organization and cell motility via Girdin/APE2005

    • Author(s)
      Enomoto A
    • Journal Title

      Dev Cell 9

      Pages: 389-402

    • 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] Mi-2beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription2005

    • Author(s)
      Shimono K
    • Journal Title

      J Biol Chem 280

      Pages: 39436-39447

    • 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 c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization2005

    • Author(s)
      Fukuda T
    • Journal Title

      Genes Cells 10

      Pages: 655-663

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein2005

    • Author(s)
      Matsuura T
    • Journal Title

      Exp Cell Res 308

      Pages: 65-77

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Microspherule protein 1, Mi-2beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription2005

    • Author(s)
      Shimono K
    • Journal Title

      J Biol Chem 280

      Pages: 39436-39447

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells2004

    • Author(s)
      Maeda K
    • Journal Title

      Biochem Biophys Res Commun 323

      Pages: 345-354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia2004

    • Author(s)
      Jijiwa M
    • Journal Title

      Mol Cell Biol 24

      Pages: 8026-8036

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region2004

    • Author(s)
      Kodama Y
    • Journal Title

      Biochem Biophys Res Commun 320

      Pages: 108-115

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of a mouse cytoskeleton-associated protein, CKAP2, with microtubule-stabilizing properties2004

    • Author(s)
      Jin Y
    • Journal Title

      Cancer Sci 95

      Pages: 815-821

    • Related Report
      2004 Annual Research Report

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

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