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増殖細胞におけるCdk2の細胞内輸送とp27によるCdk2活性の制御機構の解明

Research Project

Project/Area Number 08F08132
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

池田 正明  Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 准教授

Co-Investigator(Kenkyū-buntansha) PHILIPPE Olivier D.L.  東京医科歯科大学, 大学院・医歯学総合研究科, 外国人特別研究員
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2009: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2008: ¥800,000 (Direct Cost: ¥800,000)
Keywords国際研究者交流 / 生化学 / サイクリン依存性キナーゼ / 細胞周期 / クロマチン / 細胞核 / CDK阻害タンパク質 / タンパク質 / フランス
Research Abstract

サイクリン依存性キナーゼ(Cdk)の一つであるCdk2は、細胞周期のG1後期からS期に活性化され、DNA複製に中心的な働きをしている。本研究は、Cdk2の核内における制御機構について新たな知見を得ることを目指している。
1.新しい核細胞質分画法の確立
従来の核細胞質分画法では、低分子量タンパク質の核外への漏出を防ぐことが出来ないことが判明した。そこで、界面活性剤の種類・濃度、塩濃度、浸透圧等の細胞溶解条件の詳細な検討をおこない、核内低分子量タンパク質の漏出が少ない核細胞質分画法を確立した。この方法は、タンパク質の核と細胞質の分布を解析するための有力な手段となると考えられる。
2.クロマチン上でのCdk2活性制御機構の解析
昨年度の解析で、クロマチン非結合Cdk2は、非イオン性界面活性剤で容易に抽出されるのに対して、クロマチン結合Cdk2は抽出されないことを見出した。さらに、クロマチン結合Cdk2が、その活性を保ったまま高塩濃度処理により抽出されることを明らかにした。そこで本年度は、核内に局在するクロマチン結合および非結合Cdk2を分離し、Cdk2の活性およびCdk2を制御する因子との相互作用を生化学的に解析した。その結果、クロマチンに結合したCdk2は、サイクリンを含むCdk2制御因子と複合体を形成していることが分かった。以上の結果からクロマチン上においてCdk2が制御を受けていることが示唆された。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (23 results)

All 2010 2009 2008

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (14 results) Book (1 results)

  • [Journal Article] Association of Caspase-8 Mutation with Chemoresistance to Cisplatin in HOC313 Head and Neck Squamous Cell Carcinoma Cells2009

    • Author(s)
      Liu J, Uematsu H, Tsuchida N, Ikeda MA
    • Journal Title

      Biochem.Biophys.Res.Commun. 390

      Pages: 989-994

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of two novel mutations and relatively high incidence of HRAS mutations in Vietnamese oral cancer2009

    • Author(s)
      Murugan AK, Hong NT, Cue TTK, Hung NC, Munirajan AK, Ikeda MA, Tsuchida N
    • Journal Title

      Oral Oncology 45

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] E2F-like elements in p27 (Kip1) promoter specifically sense deregulated E2F activity2009

    • Author(s)
      Ozono E, Komori H, Iwanage R, Ikeda MA, Iseki S, Ohtani K
    • Journal Title

      Genes Cells 14

      Pages: 89-99

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the cyclin D2 and cdk6 genes through NF-kB is critical for cell cycle progression induced by HTLV-I Tax2008

    • Author(s)
      Iwanaga R, Ozono E, Fujisawa J, Ikeda MA, Okamura N, Huang Y, Ohtani K
    • Journal Title

      Oncogene 27

      Pages: 5635-5642

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] E2F-like elements in p27(Kip1) promoter specifically sense deregulated E2F activity2008

    • Author(s)
      Ozono E, Komori H, Iwanaga R, Ikeda, MA, Iseki S, Ohtani K
    • Journal Title

      Genes Cells 14

      Pages: 89-99

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor Growth Suppression by the Coactivator p3002008

    • Author(s)
      Suganuma T, Ikeda MA
    • Journal Title

      J. Oral Biosci. 50

      Pages: 115-124

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Defect in Ser46 Phosphorylation of p53 Protein : A Resistance Mechanism against p53 Gene Transfer in Oral Squamous Cell Carcinoma Cells2008

    • Author(s)
      Ichwan, SJA, Ikeda MA
    • Journal Title

      J. Oral Biosci. 50

      Pages: 98-106

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Inhibitory effect of CT domain of CCN3/NOV on proliferation and differentiation of osteogenic mesenchymal stem cells, Kusa-A12008

    • Author(s)
      Katsuki Y, Sakamoto K, Minamizato T, Makino H, Umezawa A, Ikeda MA, Perbal B, Amagasa T, Yamaguchi A, Katsube K
    • Journal Title

      Biochem. Biophys. Res. Commun. 568

      Pages: 808-814

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cyclin E expression in early neural stem cells during adult hippocampal neurogenesis2010

    • Author(s)
      Yayoi Ikeda, Masahiko Takiguchi, Masa-Aki Ikeda
    • Organizer
      Keystone Symposia "Stem Cell Differentiation and Dedifferentiation"
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] A Novel Mechanism for Regulation P53 Tumor Suppressor and Its Dysregulation in Oral Cancer2009

    • Author(s)
      Ikeda, MA
    • Organizer
      The 15th Scientific and Refersher Course in Dentistry (KPPIKG 2009)
    • Place of Presentation
      Jakarta, Indonesia
    • Year and Date
      2009-10-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Anti-cancer properties of and Thymoquinone, constituents of Nigella sativa, on oral cancer cell lines2009

    • Author(s)
      Ichwan Solachuddin J.A., Muhammad Taher, Widya Lestari, M.Termidzi Junaidi, Masa-Aki Ikeda
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Drug-specific Effects of Caspast-8 and p53/p73 Alterations on Chemosensitivity in Head and Neck Carcinoma Cells2009

    • Author(s)
      Juan Liu, Nobuo Tsuchida, Masa-Aki Ikeda
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Spatiotemporal analysis of Cdk2 interraction with its regulatory proteins2009

    • Author(s)
      Philippe Olivier D.L., Masa-Aki Ikeda
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effect of Nutlin-3 on p53 resistance in tumor cells lacking the ability to phosphorylate Ser46 on p532009

    • Author(s)
      Teng Ma, Shumpei Yamada, Ichwan Solachuddin J.A., Megumi Ostu, Kiyoshi Ohtani, Masa-Aki Ikeda
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Chemoresistance of a head and neck squamous cell carcinoma cell line carrying caspase 8 mutation2008

    • Author(s)
      Juan Liu, Nobuo Tsuchida, Hirosi Uematsu, Masa-Aki Ikeda
    • Organizer
      日中歯科医学大会2008
    • Place of Presentation
      西安、中国
    • Related Report
      2008 Annual Research Report
  • [Presentation] Expression of estrogen receptors during postnatal development of the brain2008

    • Author(s)
      Ikeda Y, Ikeda MA
    • Organizer
      EHRLICH II, 2nd World Conference on Magic Bullets
    • Place of Presentation
      Nurnberg, Germany
    • Related Report
      2008 Annual Research Report
  • [Presentation] Role of caspase-8 mutation in chemosensitivity of HOC313 oral squamous cell carcinoma cell line2008

    • Author(s)
      Liu J, Tsuchida N, Ikeda MA
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Role of DRIL1 in p53-target gene expression and p53-mediated apoptosis2008

    • Author(s)
      Ichwan SJA, Otsu M, Lestari W, Yamada S, Ikeda MA
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] The Cdk inhibitor p27/KIP1 gene senses pRB dysfunction through E2F2008

    • Author(s)
      Ozono E, Ikeda MA, Ohtani K
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Spatiotemporal dynamics of Cdk2 regulation in the cell cycle2008

    • Author(s)
      Olivier DL Philippe, Shameen K Saadat, Ikeda MA
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] DRIL1によるp53のフィードバック制御2008

    • Author(s)
      乙津めぐみ, Solachuddin J. A. Ichwan, Widya Lestari, 山田俊平, 池田正明
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] 転写因子E2Fによる癌性変化と増殖刺激の識別2008

    • Author(s)
      大園瑛子, 池田正明, 井関祥子, 大谷清
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Book] Distinct transcriptional regulation by E2F in cell growth and tumor suppression2008

    • Author(s)
      Ohtani K, Komoril H, Ozono K, Ikeda MA, Iwanaga R.
    • Publisher
      Transworld Research Network(印刷中)
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2024-03-26  

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