Analysis of the role of protein-protein interaction for the cell cycle progression using small molecule inhibitors

• Project/Area Number: 19570193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: WATANABE Nobumoto The Institute of Physical and Chemical Research, 化合物バンク評価研究チーム, 先任研究員 (90221689)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞周期 / Plk1 / PBD / タンパク質リン酸化 / タンパク質間相互作用 / タンパク質相互作用

Research Abstract

蛍光タンパク質標識PBDとその標的リン酸化ペプチドの結合を蛍光プレートリーダーで定量する系を構築し、PBD依存結合を阻害する小分子を化合物ライブラリーから探索しpurpurogallin(PPG)を見出した。PPGは、試験管内でPBDと標的タンパク質(Wee1)の結合を1μMでほぼ完全に阻害した。PPGを用いた解析で、PBDに依存した結合は、Plk1の細胞分裂における種々の役割の中でも、特に分裂中期における染色体の整列に最も重要な役割を有することが明らかになった。

Research Products

• [Journal Article] Deficiency in chromosome congression by the inhibition of PLK1 polo box domain-dependent recognition (2009)
  • Author(s): Watanabe, N (7人中1番目)
  • Journal Title: J Biol. Chem. 284 Pages: 2344-2353
  • Peer Reviewed
• [Journal Article] Polo-like kinase 1 phosphorylates and regulates Bcl-xL during pironetin-induced apoptosis (2009)
  • Author(s): Watanabe, N (7人中6番目)
  • Journal Title: Oncogene 28 Pages: 107-116
  • Peer Reviewed
• [Journal Article] 癌細胞の細胞周期異常 (2009)
  • Author(s): 渡邉信元, 長田裕之
  • Journal Title: 日本臨牀 67 Pages: 71-76
• [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, 107-116 (2009) 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] 癌細胞の細胞周期異常 (2009)
  • Author(s): 渡邉信元
  • Journal Title: 日本臨牀 67 Pages: 71-76
• [Journal Article] The regulatory βsubunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis (2008)
  • Author(s): Watanabe, N (5人中4番目)
  • Journal Title: Oncogene 27 Pages: 4986-4997
  • Peer Reviewed
• [Journal Article] Human immunodeficiency virus type 1 Vpr binds to the N lobe of the Wee1 kinase domain and enhances kinase activity for CDC2 (2008)
  • Author(s): Watanabe, N (4人中2番目)
  • Journal Title: J Virol. 82 Pages: 5672-5682
  • Peer Reviewed
• [Journal Article] Fbxw7 acts as an E3 Ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation (2008)
  • Author(s): Watanabe, N (6人中4番目)
  • Journal Title: J Biol. Chem. 283 Pages: 30540-30548
  • Peer Reviewed
• [Journal Article] Wee1 (2008)
  • Author(s): Watanabe, N
  • Journal Title: UCSD-Nature Molecule Pages Pages: 0-0
  • URL: http://www.signaling-gateway.org/molecule/query?afcsid=A002371
  • Peer Reviewed
• [Journal Article] The regulatory β-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis (2008)
  • Author(s): Yde, CW, et al
  • Journal Title: Oncogene 27 Pages: 4986-4997
  • Peer Reviewed
• [Journal Article] Human immunodeficiency virus type 1 Vpr binds to the N lobe of the Wee1 kinase domain and enhances kinase activity for CDC2 (2008)
  • Author(s): Kamata, M, et al
  • Journal Title: J Virol. 82 Pages: 5672-5682
  • Peer Reviewed
• [Journal Article] Fbxw7 acts as an E3 Ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation (2008)
  • Author(s): Kanei-Ishii, C, et al
  • Journal Title: J Biol. Chem. 283 Pages: 30540-30548
  • Peer Reviewed
• [Journal Article] Wee1 (2008)
  • Author(s): Watanabe, N
  • Journal Title: UCSD-Nature Molecule Pages http://www.signaling-gateway.org/molecule/query?afcsid=A002371
  • Peer Reviewed
• [Journal Article] 染色体複製から分裂開始までを監視するチェックポイント経路-その活性化と不活性化の分子機構- (2007)
  • Author(s): 渡辺 信元
  • Journal Title: 実験医学 25 Pages: 662-670
• [Presentation] SCFbeta-TrCPによるCdc25Bの制御 (2008)
  • Author(s): 内田 早苗
  • 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 (BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] SCFbeta-TrCPによるCdc25Bの制御 (2008)
  • Author(s): 内田早苗
  • 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(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 小分子阻害剤を用いた細胞分裂におけるPBD依存性結合の役割の解析 (2008)
  • Author(s): 渡邉 信元
  • 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 (BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 小分子阻害剤を用いた細胞分裂におけるPBD依存性結合の役割の解析 (2008)
  • Author(s): 渡邉信元
  • 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(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 小分子阻害剤によるPlk1ポロボックス依存性結合の細胞分裂進行における役割の解析 (2008)
  • Author(s): 渡邉 信元
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Small molecule inhibitors of phosphorylation dependent protein-protein interactions (2008)
  • Author(s): 渡邉 信元
  • Organizer: Friday seminar by USM visiting professors
  • Place of Presentation: Univ. Sains, Malaysia, Penang
  • Year and Date: 2008-07-25
• [Presentation] Development of a screening system for HIV-1 Vpr Inhibitors and the study of its mechanism of action (2008)
  • Author(s): Eugene Ong
  • Organizer: 4th Korea-Japan Chemical Biology Symposium
  • Place of Presentation: 日光
  • Year and Date: 2008-05-21
• [Presentation] 細胞分裂期進行におけるPlk1ポロボックスドメイン依存性結合の役割の化学生物学的解析 (2008)
  • Author(s): 渡邉信元
  • Organizer: 日本ケミカルバイオロジー研究会第3回年会
  • Year and Date: 2008-05-19
• [Presentation] Plk1のポロボックスドメイン依存結合は分裂中期染色体の速やかな整列に必要である (2007)
  • Author(s): 渡辺 信元
  • 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: パシフィコ横浜,横浜
  • Year and Date: 2007-12-12
• [Presentation] Small Molecule inhibitors for Polo Box Domain Dependent Recognition (2007)
  • Author(s): Nobumoto Watanabe
  • Organizer: AACR-NCI-EORTC International Conference Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Moscone West ConventionCenter,San Francisco,米国
  • Year and Date: 2007-10-23
• [Presentation] Screening for small molecule inhibitors of polo box domain dependent recognition (2007)
  • Author(s): Nobumoto Watanabe
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜,横浜
  • Year and Date: 2007-10-05
• [Presentation] Identification of Small Molecule Inhibitors of Polo Box Domain Dependent Recognition (2007)
  • Author(s): Nobumoto Watanabe
  • Organizer: the 5th Salk Institute Cell Cycle Meeting
  • Place of Presentation: Salk Inst.San Diego,米国
  • Year and Date: 2007-07-15
• [Remarks]
  • URL: http://www.antibiotics.riken.jp