Inhibitory mechanism of p53 transactivation by anaplastic lymphoma kinase(ALK) through direct p53 tyrosine phosphorylation

• Project/Area Number: 21370083
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: ENARI Masato 独立行政法人国立がん研究センター, 研究所, ユニット長 (90294058)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 転写 / 癌 / 遺伝子 / シグナル伝達

Research Abstract

Certain chromosomal translocations have been found in lymphomas and lung cancers and their translocations are known to promote tumor formation. We found that translocated genes have both abilities to activate oncogenic factors and to inactivate tumor suppressors. Moreover, we found that pathologically activated genes by translocations inhibit an important tumor suppressor through its direct phosphorylations and that these phosphorylations inactivate the tumor-suppressive function through enhancement of cytoplasmic retention of the tumor suppressor.

Research Products

• [Journal Article] KIF5B-RET fusions in lung adenocarcinoma (2012)
  • Author(s): Takashi Kohno, Hitoshi Ichikawa, Yasushi Totoki, Kazuki Yasuda, Masaki Hiramoto, Takao Nammo, Hiromi Sakamoto, Koji Tsuta, Koh Furuta, Yoko Shimada, Reika Iwakawa, Hideaki Ogiwara, Takahiro Oike, Masato Enari, Aaron J. Schetter, Hirokazu Okayama, Aage Haugen, Vidar Skaug, Suenori Chiku, Itaru Yamanaka, Shun-ichi Watanabe, Ikuo Sekine, Seishi Ogawa, Curtis C. Harris, Hitoshi Tsuda, Teruhiko Yoshida, Jun Yokota and Tatsuhiro Shibata
  • Journal Title: Nat. Med. Volume: 18 Pages: 375-377
• [Journal Article] Overexpression of DNA sensor proteins, AIM2 and IFI16, contributes to tumorigenesis of OSCC with p53 inactivation (2012)
  • Author(s): Yuudai Kondo, Kentaro Nagai, Shingo Nakahata, Yusuke Saito, Tomonaga Ichikawa, Akira Suekane, Tomohiko Taki, Reika Iwakawa, Masato Enari, Masafumi Taniwaki, Jun Yokota, Sumio Sakoda and Kazuhiro Morishita
  • Journal Title: Cancer Sci. Volume: 103 Pages: 782-790
• [Journal Article] KIF5B-RET fusions in lung adenocarcinoma (2012)
  • Author(s): Takashi Kohno, et al
  • Journal Title: Nat.Med. Volume: 18 Pages: 375-377
  • Peer Reviewed
• [Journal Article] Prevalence of Human Papillomavirus 16/18/33 Infection and p53 Mutation in Lung Adenocarcinoma (2010)
  • Author(s): Reika Iwakawa, Takashi Kohno, Masato Enari, Tohru Kiyono, and Jun Yokota
  • Journal Title: Cancer Sci. Volume: 101 Pages: 1891-1896
  • NAID: 10027830870
• [Journal Article] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences (2010)
  • Author(s): Masami Kodama, Chihiro Otsubo, Toru Hirota, Jun Yokota, Masato Enari, and Yoichi Taya
  • Journal Title: Mol. Cell. Biol. Volume: 30 Pages: 1620-1633
• [Journal Article] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences (2010)
  • Author(s): Masami Kodama, et al.
  • Journal Title: Mol.Cell.Biol. Volume: 30 Pages: 1620-1633
  • Peer Reviewed
• [Journal Article] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences (2010)
  • Author(s): Masami Kodama, et al.
  • Journal Title: Mol.Cell.Biol. 30 Pages: 1620-1633
  • Peer Reviewed
• [Journal Article] Identification of a function-specific mutation of clathrin heavy chain(CHC) required for p53 transactivation (2009)
  • Author(s): Hirokazu Ohata, Nobuyuki Ota, Mikako Shirouzu, Shigeyuki Yokoyama, Jun Yokota, Yoichi Taya and Masato Enari
  • Journal Title: J. Mol. Biol. Volume: 394 Pages: 460-471
• [Journal Article] Identification of a function-specific mutation of clathrin heavy chain(CHC)required for p53 transactivation (2009)
  • Author(s): Hirokazu Ohata, et al.
  • Journal Title: J.Mol.Biol. 394 Pages: 460-471
  • Peer Reviewed
• [Presentation] p53不活性化による細胞の運動能と浸潤能の制御機構に関する研究 (2011)
  • Author(s): 大坪千裕、岩川麗香、市川仁、清野透、横田淳、江成政人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] ALKによるp53不活性化機構 (2011)
  • Author(s): 江成政人、大坪千裕、田矢洋一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] p53は癌におけるALK融合蛋白質によるチロシン残基リン酸化で失活する (2011)
  • Author(s): 田矢洋一,江成政人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] p53は癌におけるALK融合蛋白質によるチロシン残基リン酸化で失活する (2011)
  • Author(s): 田矢洋一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2011-10-03
• [Presentation] ATMによるp53Ser46の直接的リン酸化 (2010)
  • Author(s): 江成政人、児玉昌美、大坪千裕、横田淳、田矢洋一
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences (2010)
  • Author(s): 江成政人、児玉昌美、大坪千裕、横田淳、田矢洋一
  • Organizer: 第15回p53国際ワークショップ
  • Place of Presentation: フィラデルフィア
  • Year and Date: 2010-10-11
• [Presentation] p53とMdmxとの相互作用を阻害する低分子化合物の同定 (2010)
  • Author(s): 江成政人、瓦谷泰之、上里新一、横田淳
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] p53による細胞運動制御機構の解析 (2009)
  • Author(s): 大坪千裕、大友亮、横田淳、江成政人
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Nuclear mitotic apparatus(NuMA)タンパク質によるp53を介した転写選択制御機構 (2009)
  • Author(s): 江成政人、大畑広和、田矢洋一
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] チロシンキナーゼALKによるp53を介した転写の抑制機構 (2009)
  • Author(s): 江成政人、吉田祐輔、横田淳、田矢洋一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Remarks]
  • URL: http://www.ncc.go.jp/jp/nccri/divisions/refractory/refractory.html
• [Patent(Industrial Property Rights)] p53-mdmx相互作用を阻害する低分子抗がん剤 (2010)
  • Inventor(s): 江成政人、上里新一
  • Industrial Property Rights Holder: 学校法人関西大学、財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-043548
  • Filing Date: 2010-02-26
• [Patent(Industrial Property Rights)] 特許権 (2010)
  • Inventor(s): 江成政人, 上里新一
  • Industrial Property Rights Holder: 学校法人関西大学財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-043548
  • Filing Date: 2010-02-26