Mitotic regulation by novel p53 target gene product

• Project/Area Number: 19770178
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Nippon Medical School
• Principal Investigator: SATO Eri Nippon Medical School, 老人病研究所, 講師 (90339440)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 細胞周期 / p53 / ユビキチンリガーゼ / DNA損傷

Research Abstract

癌抑制因子p53の発現レベルは通常非常に低く保たれているが、DNA損傷などのストレス刺激や癌遺伝子の活性化などにより安定化され転写調節因子として標的遺伝子の発現を誘導し、細胞周期の停止、DNA修復、アポトーシスの誘導を行うことが知られている。本研究で、DNA損傷時に、p53依存的にCullin3を中心とする複合体型E3ユビキチンリガーゼのサブユニットであるクローン#130の発現が誘導され、基質である#130-BP1をプロテアソーム分解経路により分解しAurora-Aを不活性化することによりG2期から分裂期への進行を抑制するという、新たな抑制機構を明らかにした。

Research Products

• [Journal Article] Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2 (2008)
  • Author(s): Abe Y, Oda-Sato E, Tobiume K, Kawauchi K, Taya Y, Okamoto K, Oren M, Tanaka N
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 4838-4843
  • Peer Reviewed
• [Journal Article] 5-Aza-2' -deoxycytidine restores proapoptotic function of p53 in cancer cells resistant to p53-induced apoptosis (2008)
  • Author(s): Yagi S, Oda-Sato E, Uehara I, Asano Y, Nakajima W, Takeshita T, Tanaka N
  • Journal Title: Cancer Invest 26 Pages: 680-688
  • Peer Reviewed
• [Journal Article] 5-Aza-2' -deoxycytidine restores proapoptotic function of p53 in cancer cells resistant to p53-induced apoptosis (2008)
  • Author(s): Shutaro Yagi
  • Journal Title: Cancer Invest 26 Pages: 680-688
  • Peer Reviewed
• [Journal Article] Hedgehog signaling overrides p53-mediated tumor suppression byactivating Mdm2. (2008)
  • Author(s): Yoshinori Abe
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 4838-4843
  • Peer Reviewed
• [Journal Article] 5-Aza-2'-deoxycytidine restores proapoptotic function of p53 in cancer cells resistant to p53-induced apoptosis. (2008)
  • Author(s): Shutaro Yagi
  • Journal Title: Cancer Invest. (印刷中)
  • Peer Reviewed
• [Journal Article] Abnormal Centrosome Amplification and Aurora-A Activation in p53-deficient Cells. (2007)
  • Author(s): Oda-Sato E, Tanaka N
  • Journal Title: J. Nippon Med. Sch. 74 Pages: 234-235
• [Journal Article] Abnormal Centrosome Amplification and Aurora-A Activation in p53-deficient Cells (2007)
  • Author(s): Eri Oda-Sato
  • Journal Title: J. Nippon Med. Sch. 74 Pages: 234-235
• [Presentation] Mitotic regulation by novel p53 target gene product (2007)
  • Author(s): 佐藤(織田)恵理
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-14
• [Presentation] Mitotic regulation by novel p53 target gene product (2007)
  • Author(s): 佐藤(織田)恵理
  • Organizer: 第30回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-14