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2005 Fiscal Year Final Research Report Summary

Study of molecular structural and dynamical aspects of transcriptional regulatory factors

Research Project

Project/Area Number 16370051
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionYokohama City University

Principal Investigator

OAGATA Kazuhiro  Yokohama City University, Biochemistry, Professor, 医学研究科, 教授 (90260330)

Co-Investigator(Kenkyū-buntansha) SATO Ko  Yokohama City University, Biochemistry, Research Associate, 医学部, 助手 (90300962)
SHIINA Masaaki  Yokohama City University, Biochemistry, Research Associate, 医学部, 助手 (30347299)
HAMADA Keisuke  Yokohama City University, Biochemistry, Research Associate, 医学部, 助手 (00344052)
Project Period (FY) 2004 – 2005
KeywordsRunx1 / Ets1 / CBFβ / enhanceosome / molecular fluctuations / phosphorylation / exon VII / NMR
Research Abstract

The goal of this project is to elucidate molecular mechanisms for regulating the enhanceosome formation, particularly, stabilization of transcription factors bound to an enhancer region of a gene.
We investigated some complexes containing a transcriptional regulatory factor, Runx1, which plays a pivotal role in hematopoiesis and is involved in acute leukemias. The DNA binding activity of Runxl is enhanced allosterically by non-DNA binding heterodimeric partner, CBFβ. Previously, we showed that there was no significant structural change of Runxl upon binding of CBFβ when a crystal structure of Runx1-DNA complex was compared with that of Runx1-CBFβ-DNA complex. It promoted us to focus on molecular fluctuations of Runx1. Magnetic relaxation measurements using NMR demonstrated that some regions of Runx1 are significantly fluctuated without CBFβ, while the fluctuations of Runx1 became reduced upon binding of CBFβ. We proposed that regulations of molecular functions are accomplished by alteri … More ng molecular fluctuations.
Runxl is also involved in transcriptional regulation of the T cell antigen receptor a chain (TCRα) together with another transcriptional regulatory factor, Etsl. The DNA binding activity of Etsl is controlled by an N-terminal flanking region of ETS domain, referred exon VII. The exon VII inhibits the DNA binding activity of Ets1 while the inhibition is released by an adjacently placed Runxl. Etsl is not capable of binding the enhancer upon phosphorylation of exon VII even if Runxl binds to the enhancer. We investigated the molecular details of the complex composed of Runxl and Etsl in the TCRα enhancer using X-ray crystallography, EMSA and the luciferase reporter gene assay. We identified which regions of Etsl are responsible for cooperative DNA binding with Runxl and the impact of the exon VII phosphorylation. Further structural analyses might be required to unveil overall aspect of the regulatory systems. We will also study about fluctuations of Runxl upon Etsl binding. Less

  • Research Products

    (5 results)

All 2007 2005

All Journal Article (4 results) Book (1 results)

  • [Journal Article] Distant N-terminal and C-terminal domains are required for intrinsic kinase activity of SMG-1, a critical component of nonsense-mediated mRNA decay2007

    • Author(s)
      Morita T
    • Journal Title

      J Biol Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Weel via multiple pathways2005

    • Author(s)
      Nobumoto Watanabe
    • Journal Title

      Proc. Natl. Acad. Sci. USA 102

      Pages: 11663-11668

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 特集 転写制御と疾患 タンパク質の分子構造異常と癌化.2005

    • Author(s)
      緒方 一博
    • Journal Title

      Molecular Medicine 42

      Pages: 64-75

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Weel via multiple pathways2005

    • Author(s)
      Nobumoto Watanabe
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 11663-11668

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 分子生物学実験シリーズ「図・写真で観るタンパク構造・機能解析実験実践ガイド」タンパク質の立体構造解析を行うために-分子構造解析のためのタンパク質試料調整法.2005

    • Author(s)
      椎名政昭
    • Total Pages
      18-32
    • Publisher
      メディカル ドゥ
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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