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2008 Fiscal Year Final Research Report

Inactivation of Tumor Suppressor Protein p53 by Mutations in the Tetramerization Domain and Stabilizing Methods for the Tetrameric Structure

Research Project

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Project/Area Number 18310140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionHokkaido University

Principal Investigator

SAKAGUCHI Kazuyasu  Hokkaido University, 大学院・理学研究院, 教授 (00315053)

Co-Investigator(Kenkyū-buntansha) TOSHIAKI Imagawa  北海道大学, 大学院・先端生命科学研究院, 准教授 (20142177)
CHUMAN Yoshiro  北海道大学, 大学院・理学研究院, 助教 (40372263)
Project Period (FY) 2006 – 2008
Keywords構造活性相関 / 蛋白質 / 癌 / バイオテクノロジー / 生体分子
Research Abstract

がん抑制遺伝子p53の変異は、ヒト悪性腫瘍で最も多く報告されている異常である。ヒトp53はリン酸化タンパク質であり、そのがん抑制機能の発現のためには四量体の形成が必須である。本研究では、四量体形成ドメイン変異や修飾によるp53機能の不活性化機構と変異の閾値を明らかとした。さらに、p53四量体ドメインに対する安定化法および機能修復ペプチドの開発を実施した。

  • Research Products

    (43 results)

All 2009 2008 2007 2006 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (26 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Oxidation of methionine residue at hydrophobic core destabilizes p53 tetrameric structure2009

    • Author(s)
      T. Nomura, R. Kamada, I. Ito, Y.Chuman, Y. Shimohigashi, K. Sakaguchi
    • Journal Title

      Biopolymers 91(1)

      Pages: 78-84

    • Peer Reviewed
  • [Journal Article] Effects of tumor-associated mutations in thep53 tetramerization domain onoligomerization state and transcriptionalactivity2009

    • Author(s)
      R. Kamada, T. Terai, T. Nomura, Y. Chuman, T. Imagawa, K. Sakaguchi
    • Journal Title

      Adv. Exp.Med. Biol 611

      Pages: 567-568

    • Peer Reviewed
  • [Journal Article] Thermal Stability of p53 Tetramerization Domain Peptides Derived from Various Species2009

    • Author(s)
      T. Nomura, R. Kamada, Y. Chumanand and K. Sakaguchi
    • Journal Title

      Peptide Sci 2008

      Pages: 35-36

    • Peer Reviewed
  • [Journal Article] Evaluation of Transcriptional Activity of p53 in Individual Living Mammalian Cell2009

    • Author(s)
      T.Imagawa, T. Terai, Y. Yamada, R. Kamada and K. Sakaguchi
    • Journal Title

      Anal. Biochem. 387

      Pages: 249-256

    • Peer Reviewed
  • [Journal Article] Differential Recognition of PhosphorylatedTransactivation Domains of p53 by Differentp300 Domains2008

    • Author(s)
      S. Polley, S. Guha, N.S. Roy,S. Kar, K. Sakaguchi, Y. Chuman, V.Swaminathan and S. Roy
    • Journal Title

      J. Mol. Biol. 376

      Pages: 8-12

    • Peer Reviewed
  • [Journal Article] Correlation of Oligomeric Structure and Transcriptional Activity of p53 Mutants2008

    • Author(s)
      R. Kamada, T. Terai, T. Nomura, Y. Chuman, T.Imagawa and K. Sakaguchi
    • Journal Title

      Peptide Sci 2007

      Pages: 69-70

    • Peer Reviewed
  • [Journal Article] Screening of Peptides to Stabilize the p53 Tetramer Formation from Phage Displayed Library2008

    • Author(s)
      T. Nomura, R. Kamada, Y. Chuman and K. Sakaguchi
    • Journal Title

      Peptide Sci 2007

      Pages: 315-316

    • Peer Reviewed
  • [Journal Article] Correlation between Expression Level in E.coli and Stability of Oligomeric Structure ofthe p53 Tetramerization Domain2008

    • Author(s)
      H. Miyazaki, R. Kamada, T. Nomura, Y. Chuman, T.Imagawa and K. Sakaguchi
    • Journal Title

      Peptide Sci 2007

      Pages: 317-318

    • Peer Reviewed
  • [Journal Article] Structural Photomodulation of Peptides with Azobenzoate Derivative in Peptide Backbone.2008

    • Author(s)
      R. Kamada, K. Fukuda, H. Miyazaki, T.Nomura, Y. Chuman, T. Imagawa, K. Tanino and K. Sakaguchi
    • Journal Title

      Peptide Sci 2007

      Pages: 447-448

    • Peer Reviewed
  • [Journal Article] Stabilization of p53 Tetrameric Structure by Polyol Compounds2007

    • Author(s)
      T. Nomura, Y. Chuman and K. Sakaguchi
    • Journal Title

      Peptide Sci 2006

      Pages: 131-132

    • Peer Reviewed
  • [Journal Article] Thermodynamic Stability of Mutant p53 Tetramerization Domain Peptides Associated with Human Tumors2007

    • Author(s)
      R. Kamada, T. Nomura, Y. chuman, T. Imagawa and K. Sakaguchi
    • Journal Title

      Peptide Sci 2006

      Pages: 131-132

    • Peer Reviewed
  • [Journal Article] Unfolding, Aggregation, and Amyloid Formation by the Tetramerization Domain from Mutant p53 Associated with Lung Cancer2006

    • Author(s)
      Y. Higashimoto, Y. Asanomi, S.Takakusagi, M. S. Lewis, K. Uosaki, S. R. Durell, C. W. Anderson, E. Appella and K. Sakaguchi
    • Journal Title

      Biochemistry 45

      Pages: 1608-1619

    • Peer Reviewed
  • [Journal Article] Analysis of Stabilization by Substituti on of Cyclohexylalanine for Phe341 in Hydrophobic Core of p53 Tetramer.2006

    • Author(s)
      T. Nomura, K. Sakamoto, Y. Kasai, Y. Chuman, K. Ishimori and K. Sakaguchi
    • Journal Title

      Peptide Science 2005

      Pages: 399-402

    • Peer Reviewed
  • [Journal Article] Fibrillar and Granular Aggregation of G334V Mutant p53 Tetramer Peptide. Y. Asanomi, Y. Higashimoto2006

    • Author(s)
      Y. Asanomi, Y. Higashimoto, Y. Chuman, S. Kaya, T. Imagawa and K. Sakaguchi
    • Journal Title

      Peptide Sci 2005

      Pages: 397-398

    • Peer Reviewed
  • [Presentation] Thermal stability of p53 tetramerization domain peptides derived from various species2008

    • Author(s)
      T. Nomura, et. al.
    • Organizer
      第45回ペプチド討論会
    • Place of Presentation
      船堀
    • Year and Date
      2008-10-29
  • [Presentation] Chemical and Structural Proteomics : The Solution to Biological Problems2008

    • Author(s)
      K. Sakaguchi
    • Organizer
      MPSA2008
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-08-26
  • [Presentation] Effect of thermodynamic stability on expression level of p53 tetramerization domain peptides in E. coli2008

    • Author(s)
      H. Miyazaki, et. al.
    • Organizer
      MPSA2008
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-08-26
  • [Presentation] Analysis of stability for p53 tetramerization domain peptides derived from various species2008

    • Author(s)
      T. Nomura, et. al.
    • Organizer
      MPSA2008
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-08-26
  • [Presentation] Tetramerization of tumor suppressor protein p532008

    • Author(s)
      K. Sakaguchi
    • Organizer
      12th Akabori Conference : German-Japanese Symposium on Peptide Science
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-16
  • [Presentation] Tetramerization Domain of Tumor Suppressor Protein p532008

    • Author(s)
      K. Sakaguchi
    • Organizer
      Taiwan-Japan International Symposium on Organic Chemistry and Molecular Science
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2008-04-18
  • [Presentation] 癌抑制タンパク質p53四量体形成ドメインペプチドの空隙充填による自己組織可能への影響2008

    • Author(s)
      野村尚生, 他
    • Organizer
      分子情報生命科学シンポジウム2008
    • Place of Presentation
      札幌
    • Year and Date
      2008-02-29
  • [Presentation] ターン部位にアゾベンゼンアミノ酸誘導体を導入したペプチドの光による構造制御2008

    • Author(s)
      中馬吉郎, 他
    • Organizer
      分子情報生命科学シンポジウム2008
    • Place of Presentation
      札幌
    • Year and Date
      2008-02-29
  • [Presentation] 大腸菌発現量におけるペプチド構造安定性の効果2008

    • Author(s)
      宮崎広充, 他
    • Organizer
      北海道支部2008 年冬季研究発表会
    • Place of Presentation
      札幌
    • Year and Date
      2008-01-29
  • [Presentation] Stability of oligomeric structure is the key factor for transcriptional activity in tumor suppressor protein p53 BMB20072007

    • Author(s)
      T. Imagawa, et. al.
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
  • [Presentation] Correlation of oligomeric Structure and Transcritional Activity of p53 Mutants2007

    • Author(s)
      坂口和靖, 他
    • Organizer
      第44回ペプチド討論会
    • Place of Presentation
      富山
    • Year and Date
      2007-11-07
  • [Presentation] Structural photomodulation of peptides with azobenzoate derivative in peptide backbone2007

    • Author(s)
      R. Kamada, et. al.
    • Organizer
      第44回ペプチド討論会
    • Place of Presentation
      富山
    • Year and Date
      2007-11-07
  • [Presentation] Correlation between expression level in E.coli and stability of oligomeric structure of the p53 tetramerization domain2007

    • Author(s)
      H. Miyazaki, et. al.
    • Organizer
      第44回ペプチド討論会
    • Place of Presentation
      富山
    • Year and Date
      2007-11-07
  • [Presentation] Screening of peptides to stabilize the p53 tetramer formation from phage displayed library formation from phage displayed library2007

    • Author(s)
      T. Nomura, et. al.
    • Organizer
      第44回ペプチド討論会
    • Place of Presentation
      富山
    • Year and Date
      2007-11-07
  • [Presentation] 癌抑制タンパク質p53四量体形成ドメイン2007

    • Author(s)
      坂口和靖
    • Organizer
      日本バイオインフォマティクス学会北海道地域部会
    • Place of Presentation
      札幌
    • Year and Date
      2007-08-03
  • [Presentation] Effects of Tumor-Associated Mutations in the p53 Tetramerization Domain on Oligomerization State and Transcriptional Activity2007

    • Author(s)
      R. Kamada, et. al.
    • Organizer
      20th American Peptide Society Symposium
    • Place of Presentation
      Montreal, Quebec, Canada
    • Year and Date
      2007-06-26
  • [Presentation] ヒト悪性腫瘍で見られる変異が癌抑制タンパク質p53四量体構造の安定性に与える影響2007

    • Author(s)
      鎌田瑠泉, 他
    • Organizer
      日本化学会第87春季年会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-25
  • [Presentation] Oligomeric Structures and Stability of Mutant p53 Tetramerization Domain Peptides Associated with Human Tumors2006

    • Author(s)
      R. Kamada, et.al.
    • Organizer
      Japan - China Joint Symposium onModern Chemistry 2nd Hokkaido University-Nanjing University joint Symposium
    • Place of Presentation
      Sapporo
    • Year and Date
      2006-11-10
  • [Presentation] Polyol Osmolytes Affect Stability and Oligomeric State of p53 Tetramerization Domain2006

    • Author(s)
      T. Nomura, et.al.
    • Organizer
      Japan-China Joint Symposium on Modern Chemistry 2nd Hokkaido University- Nanjing University joint Symposium
    • Place of Presentation
      Sapporo
    • Year and Date
      2006-11-10
  • [Presentation] Stabilization of p53 Tetrameric Structure by Polyol Compounds2006

    • Author(s)
      T. Nomura, et.al.
    • Organizer
      第43回ペプチド討論会
    • Place of Presentation
      横浜
    • Year and Date
      2006-11-05
  • [Presentation] Thermodynamic stability of mutant p53 tetramerization domain peptides associated with human tumors2006

    • Author(s)
      R. Kamada, et.al.
    • Organizer
      第43回ペプチド討論会
    • Place of Presentation
      横浜
    • Year and Date
      2006-11-05
  • [Presentation] Stabilization of p53 Tetramerization Domain by Occupying Cavities with Cyclohexylalanine2006

    • Author(s)
      T. Nomura, et. al.
    • Organizer
      The 20th symposium of the protein society
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2006-08-05
  • [Presentation] Amyloid formation of mutant p53 peptide was affected by hetero-oligomerization with the wild-type peptide2006

    • Author(s)
      Y. Asanomi, et.al.
    • Organizer
      The 20th symposium of the protein society
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2006-08-05
  • [Presentation] Effects of Mutation in p53 tetramerization domain on oligomeric structure and stability2006

    • Author(s)
      R. Kamada, et. al.
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
  • [Presentation] Stabilization by substitution of cyclohexylalanine for phe341 in hydrophobic core of p53 tetramer2006

    • Author(s)
      T. Nomura, et. al.
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
  • [Presentation] Correlation Between Stability of Oligomeric Structure and Transcriptional Activity in Tumor Suppressor Protein p53 Mutants2006

    • Author(s)
      T. Terai, et. al.
    • Organizer
      20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-06-18
  • [Remarks]

    • URL

      http://barato.sci.hokudai.ac.jp/~biochem/index.html

  • [Patent(Industrial Property Rights)] プロテインホスファターゼ阻害剤2008

    • Inventor(s)
      坂口和靖, 谷野圭持, 中馬吉郎, 吉村文彦, 八木寛陽
    • Industrial Property Number
      特願2008-262646
    • Filing Date
      2008-10-09
  • [Patent(Industrial Property Rights)] p53翻訳後修飾部位を特異的に認識するーナル抗体、及びその抗体を含む修飾部位測定キット2006

    • Inventor(s)
      坂口和靖, 中馬吉郎, 明日山康生, 松木園美穂
    • Industrial Property Number
      PCT/JP2006/306921,特願2007-511193
    • Filing Date
      2006-03-31

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Published: 2010-06-10   Modified: 2016-04-21  

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