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

2011 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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] 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] 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
• [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] 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] 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
• [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
  • Total Pages: 58-63
  • 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
  • Total Pages: 19-26
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/asi/cl-vali/index.html