Analyses of the role of peptidyl prolyl isomerase on the cell cycle progression through small moleule inhibitors

• Project/Area Number: 21603017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: WATANABE Nobumoto 独立行政法人理化学研究所, 化合物ライブラリー評価研究チーム, チームヘッド (90221689)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: タンパク質リン酸化 / イソメラーゼ / 脱リン酸化酵素 / 細胞周期 / Pin1 / タンパク質間相互作用 / タンパク質乾燥後作用

Research Abstract

We have established a simple screening system for Pin1 inhibitor through the measurement of the binding of the fluorescence protein tagged Pin1 and phosphorylated target peptides. We have successfully isolated Pin 1 inhibitors and analyzed the role of Pin1 on the cell cycle progression using them. Pin1 was found to be important for the exit of mitosis.

Research Products

• [Journal Article] SCF β TrCP mediates stress-activated MAP kinase-induced Cdc25B degradation. (2014)
  • Author(s): Uchida, S, et al.
  • Journal Title: J Cell Sci. Volume: 124 Issue: 16 Pages: 2816-2825
  • DOI: 10.1242/jcs.083931
  • Peer Reviewed
• [Journal Article] Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity in spite of close relationship to acyl protein thioesterases (2012)
  • Author(s): Burger, M., Zimmermann, TJ., Kondoh, Y., Stege, P., Watanabe, N., Osada, H., Waldmann, H., and Vetter, IR.
  • Journal Title: J Lipid Res Volume: 53 Pages: 43-50
  • Peer Reviewed
• [Journal Article] Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases (2012)
  • Author(s): Burger, M., Zimmermann, T. J., Kondoh, Y., Stege, P., Watanabe, N., Osada, H., Waldmann, H. & Vetter, I. R
  • Journal Title: Journal of Lipid Research Volume: 53 Issue: 1 Pages: 43-50
  • DOI: 10.1194/jlr.m019851
  • Peer Reviewed
• [Journal Article] SCFβTrCP mediates stress-activated MAP kinase-induced Cdc25B degradation (2011)
  • Author(s): Uchida, S., Watanabe, N., Kudo, Y., Yoshioka, K., Matsunaga, T., Ishizaka, Y., Nakagama, H., Poon, R. Y. C., and Yamashita, K.
  • Journal Title: J. Cell Science Volume: 124 Pages: 2816-2825
  • Peer Reviewed
• [Journal Article] A coumarin-based HIV-1 VPR inhibitor, interacts with a hydrophobic region of VPR (2011)
  • Author(s): Ong, EB., Watanabe, N., Saito, A., Futamura, Y., Abd El Galil, K. H., Koito, A., Najimudin, N., Osada, H. Vipirinin
  • Journal Title: J Biol. Chem. Volume: 286 Pages: 14049-14056
  • Peer Reviewed
• [Journal Article] Vipirinin, a coumarin-based HIV-1 Vpr inhibitor, interacts with a hydrophobic region of VPR (2011)
  • Author(s): Ong E. B., et al.
  • Journal Title: J Biol Chem. Volume: 286 Issue: 16 Pages: 14049-14056
  • DOI: 10.1074/jbc.m110.185397
  • Peer Reviewed
• [Journal Article] Mapping of the interaction sites between Wee1 kinase and the regulatory b-subunit of protein kinase CK2 (2010)
  • Author(s): Olsen, BB., Kreutzer, N., Watanabe, N., Holm, T. Guerra, B.
  • Journal Title: Int. J. Oncol. Volume: 36 Pages: 1175-1182
  • Peer Reviewed
• [Journal Article] Mapping of the interaction sites between Wee1 kinase and the regulatory beta-subunit of protein kinase CK2 (2010)
  • Author(s): Olsen Birgitte B
  • Journal Title: International Journal of Oncology Volume: 36 Pages: 1175-1182
  • Peer Reviewed
• [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis (2009)
  • Author(s): Tamura, Y., Simizu, S., Muroi, M., Takagi, S., Kawatani, M., Watanabe, N., and Osada, H.
  • Journal Title: Oncogene Volume: 28 Pages: 107-116
  • Peer Reviewed
• [Journal Article] Deficiency in chromosome congression by the inhibition of PLK1 polo box domain-dependent recognition (2009)
  • Author(s): Watanabe, N., Sekine, T., Takagi, M., Iwasaki, J., Imamoto, N., Kawasaki, H. and Osada, H.
  • Journal Title: J Biol. Chem. Volume: 284 Pages: 2344-2353
  • Peer Reviewed
• [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-x_L during pironetin-induced apoptosis (2009)
  • Author(s): Tamura, Y., et al
  • Journal Title: Oncogene 28 Pages: 107-116
  • Peer Reviewed
• [Journal Article] Deficiency in chromosome congression by the inhibition of PLK1 polo box domain-dependent recognition (2009)
  • Author(s): Watanabe, N., et al
  • Journal Title: J.Biol.Chem. 284 Pages: 2344-2353
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 渡辺信元
  • Journal Title: がん化学療法・分子標的治療 update 第2章 がん化学療法の標的 3. 細胞周期(中外医学社) Pages: 19-26
• [Journal Article] Mapping of the interaction sites between Weel kinase and the regulatory beta-subunit of protein kinase CK2
  • Author(s): Olsen, B., et al
  • Journal Title: Int.J.Oncology (in press)
  • Peer Reviewed
• [Presentation] Role of peptidyl prolyl cis-trans isomerase Pin1 on M-phase progression (2011)
  • Author(s): 渡邉信元ら
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-12-16
• [Presentation] 新規リン酸化反応による分裂期キナーゼPlk1の活性制御メカニズム (2011)
  • Author(s): 笠原広介, ら
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-12-15
• [Presentation] プロリン異性化酵素Pin1の小分子阻害剤の分裂期進行への影響の解析 (2011)
  • Author(s): 渡邉信元ら
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2011-10-03
• [Presentation] Validation of NPDepo compounds through various assay systems (2011)
  • Author(s): 近藤恭光, ら
  • Organizer: 京都大学グローバルCOE-基幹研究所合同シンポジウム
  • Place of Presentation: 理研(和光市)
• [Presentation] 新しいHIV-1Vpr阻害小分子によるVprの活性部位解析 (2010)
  • Author(s): Eugene Ong
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] SCFβTrCPによるCdc25B分解におけるPEST配列の役割 (2010)
  • Author(s): 内田早苗
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Role of phosphorylation dependent protein-protein interaction on the cell cycle progression (2010)
  • Author(s): Nobumoto Watanabe
  • Organizer: MEXT Priority Research Project "Cell Proliferation Control" International Symposium Cell Cycle and Cell Differentiation From A to Z
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-04
• [Presentation] 小分子阻害剤を用いたPin1のM期進行への役割の解析 (2010)
  • Author(s): 渡邉信元
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 14-3-3タンパク質阻害小分子探索系の構築 (2010)
  • Author(s): 真田英美子
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-08
• [Presentation] リン酸化特異的プロリン異性化酵素Pin1阻害小分子の探索 (2010)
  • Author(s): 渡邉信元ら
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-07
• [Presentation] RIKEN NPDepoから単離した新しいHIV-1Vpr阻害小分子とその構造活性相関解析 (2010)
  • Author(s): Eugene Ong
  • Organizer: 日本ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-18
• [Presentation] A small molecule inhibitor of phosphorylation-dependent protein-protein interaction (2010)
  • Author(s): 渡辺信元., et al.
  • Organizer: 8th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
  • Place of Presentation: ハワイ州、ワイコロア
  • Year and Date: 2010-02-09
• [Presentation] Role of peptidyl prolyl isomerization during M-phase progression (2009)
  • Author(s): 渡辺信元, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] ポロボックス領域依存結合を阻害する小分子化合物の探索 (2009)
  • Author(s): 渡辺信元, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-02
• [Book] 細胞分裂期を制御する蛋白質分解システム (2010)
  • Author(s): 渡邉信元
  • Publisher: 共立出版
• [Book] がん化学療法・分子標的治療update第2章がん化学療法の標的3.細胞周期 (2009)
  • Author(s): 渡辺信元、長田裕之
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/asi/cl-vali/index.html