Molecular mechanisms for p53 inactivation by EHF in colorectal cancer.

• Project/Area Number: 25830073
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: TANIUE Kenzui 東京大学, 分子細胞生物学研究所, 助教 (90648627)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: EHF / p53 / MDM2 / ユビキチン化 / FOSL1 / KMT2D / 転写制御 / ヒストン修飾 / アポトーシス / ユビキチン制御

Outline of Final Research Achievements

We revealed that FOSL1 and KMT2D, a histone H3K4 methyltransferase, regulated the expressionof EHF in colorectal cancer cells. Moreover, we found that FOSL1 and KMT2D were required for the proliferation of colon cancer cells. Furthermore, we show that EHF knockdown stabilizes p53 protein. In addition, EHF interacts with and stabilizes the MDM2, a ubiquitin ligase, by interfering with its ubiquitination, which in turn destabilizes p53 protein. Finally, we identified RAD18 as a novel ubiquitinase for MDM2.

Research Products

• [Journal Article] Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells (2015)
  • Author(s): Hironobu Sugimasa, Kenzui Taniue, Akiko Kurimoto, Yasuko Takeda, Yoshihiro Kawasaki, Tetsu Akiyama
  • Journal Title: Biochemical and Biophysical Research Communications Volume: Volume 459, Issue 1 Issue: 1 Pages: 29-35
  • DOI: 10.1016/j.bbrc.2015.02.043
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Susceptibility to proteases of anti-Tn-antigen MLS128 binding glycoproteins expressed in human colon cancer cells (2015)
  • Author(s): Oura, F., Yajima, Y., Nakata, M., Taniue, K., Akiyama, T., Nakada, H., Yamamoto, K., Fujita-Yamaguchi, Y
  • Journal Title: BioScience Trends Volume: 9 Issue: 1 Pages: 49-55
  • DOI: 10.5582/bst.2014.01127
  • NAID: 130005054681
  • ISSN: 1881-7815, 1881-7823
  • Peer Reviewed
• [Journal Article] PCDH10 is required for the tumorigenicity of glioblastoma cells (2014)
  • Author(s): Kanae Echizen, Mitsutoshi Nakada , Tomoatsu Hayashi, Hemragul Sabit, Takuya Furuta, Miyuki Nakai, Ryo Koyama-Nasu, Yukiko Nishimura, Kenzui Taniue, Yasuyuki Morishita, Shinji Hirano, Kenta Terai, Tomoki Todo, Yasushi Ino, Akitake Mukasa, Shunsaku Takayanagi, Ryohei Ohtani, Nobuhito Saito, Tetsu Akiyama
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 444 Issue: 1 Pages: 13-18
  • DOI: 10.1016/j.bbrc.2013.12.138
  • Peer Reviewed / Open Access
• [Journal Article] The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumorigenesis (2014)
  • Author(s): Tsuji S
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 3150-3150
  • DOI: 10.1038/ncomms4150
  • Peer Reviewed / Open Access
• [Journal Article] The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells (2013)
  • Author(s): R Koyama-Nasu, R Haruta, Y Nasu-Nishimura, K Taniue, Y Katou, K Shirahige, T Todo, Y Ino, A Mukasa, N Saito, M Matsui, R Takahashi, A Hoshino-Okubo, H Sugano, E Manabe, K Funato and T Akiyam
  • Journal Title: Oncogene Volume: 33 Issue: 17 Pages: 2236-2244
  • DOI: 10.1038/onc.2013.168
  • Peer Reviewed / Open Access
• [Journal Article] ASBEL, an ANA/BTG3 antisense transcript required for tumorigenicity of ovarian carcinoma (2013)
  • Author(s): Yanagida S, Taniue K, Yamamoto T. (9名)
  • Journal Title: Sci Rep Volume: Vol.3 Issue: 1 Pages: 1305-1305
  • DOI: 10.1038/srep01305
  • Peer Reviewed
• [Presentation] ASBEL, an ANA/BTG3 antisense transcript required for tumorigenicity of ovarian carcinoma (2013)
  • Author(s): Kenzui Taniue, Tetsu Akiyama (Dept.Mol.Info., Inst. Mol. Cel. Bio.,Tokyo Univ.)
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] The role of miR-363-GATA6-Lgr5 pathway in colorectal tumorigenesis (2013)
  • Author(s): Yoshihiro Kawasaki1, Shinnosuke Tsuji1, Shiori Furukawa1, Kenzui Taniue1, Tomoatsu Hayashi1, Masaya Hiyoshi2, Joji Kitayama2, Tetsu Akiyama1 (1Inst. Mol. Cell. Biosci., The Univ. of Tokyo, 2Sch. Med., The Univ. of Tokyo)"
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Novel lncRNAs in Cancer
  • Author(s): Kenzui Taniue
  • Organizer: 理研セミナー
  • Place of Presentation: 理化学研究所横浜事業所
  • Invited