Regulatory mechanism of p53 deubiquitinating enzyme USP7

• Project/Area Number: 25830078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: KATO Takuya 名古屋大学, 医学(系)研究科(研究院), 特任助教 (00551970)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: USP7 / RFP / p53 / SUMO化

Outline of Final Research Achievements

We found that a SUMO E3 ligase RFP and de-ubiquitiantion enzyme USP7 stabilise p53 protein through their interaction. USP7 contribute to the stabilisation of RFP and stabilised RFP SUMOylate p53 at lysine 386 residue. We further showed that both USP7 and RFP confer cancer cells resistance to UV-induced apoptosis in a p53 expression dependent manner. These data suggest that USP7 and RFP increase the cell survival during DNA damage by stabilising p53 protein.

Research Products

• [Journal Article] Akt-girdin signaling in cancer-associated fibroblasts contributes to tumor progression (2015)
  • Author(s): Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi
  • Journal Title: Cancer Research Volume: 75 Issue: 5 Pages: 813-823
  • DOI: 10.1158/0008-5472.can-14-1317
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency (2015)
  • Author(s): Kiyota A, Iwama S, Sugimura Y, Takeuchi S, Takagi H, Iwata N, Nakashima K, Suzuki H, Nishioka T, Kato T, Enomoto A, Arima H, Kaibuchi K, Oiso Y.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 153-160
  • DOI: 10.1507/endocrj.EJ14-0369
  • NAID: 130004700287
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin. (2014)
  • Author(s): Liang Weng, Atsushi Enomoto, Hiroshi Miyoshi, Kiyofumi Takahashi, Naoya Asai, Nobuhiro Morone, Ping Jiang, Jian An, Takuya Kato, Keisuke Kuroda, Takashi Watanabe, Masato Asai, Maki Ishida-Takagishi, Yoshiki Murakumo, Hideki Nakashima, Kozo Kaibuchi and Masahide Takahashi.
  • Journal Title: EMBO Journal. Volume: 33 Issue: 18 Pages: 2098-2112
  • DOI: 10.15252/embj.201488289
  • Peer Reviewed / Open Access
• [Journal Article] TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives. (2014)
  • Author(s): Takuya Kato, Atsushi Enomoto, Takashi Watanabe, Hisashi Haga, Sumire Ishida, Yuji Kondo, Koichi Furukawa, Takeshi Urano, Shinji Mii, Liang Weng, Maki Ishida-Takagishi, Masato Asai, Naoya Asai, Kozo Kaibuchi, Yoshiki Murakumo, Masahide Takahashi.
  • Journal Title: Cell reports. Volume: 7 Issue: 4 Pages: 1156-1167
  • DOI: 10.1016/j.celrep.2014.03.068
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells. (2014)
  • Author(s): Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 5 Pages: 545-52
  • DOI: 10.1111/cas.12390
  • Peer Reviewed / Open Access
• [Journal Article] Detection of a Soluble Form of CD109 in Serum of CD109 Transgenic and Tumor Xenografted Mice. (2014)
  • Author(s): Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e83385-e83385
  • DOI: 10.1371/journal.pone.0083385
  • Peer Reviewed
• [Journal Article] The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse. (2013)
  • Author(s): Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., Murakumo, Y.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 15 Pages: 10459-10471
  • DOI: 10.1074/jbc.m112.421966
  • Peer Reviewed
• [Presentation] TRIM27 - USP7 による p53 制御機構の解明 (2014)
  • Author(s): 加藤 琢哉、榎本 篤、浅井 真人、浅井 直也、高橋 雅英
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24
• [Presentation] Mechanisms underlying the integrin beta1 expression that define heterogeneity in migrating cancer cell collectives (2013)
  • Author(s): Takuya Kato, Atsushi Enomoto, Masato Asai, Naoya Asai, Masahide Takahashi
  • Organizer: American Society for Cell Biology 2013 Annual Meeting
  • Place of Presentation: アメリカ合衆国、ニューオーリンズ
• [Presentation] がん細胞集団におけるLeadin Cellを規定する分子機構の解明 (2013)
  • Author(s): 加藤 琢哉、榎本 篤、浅井 真人、浅井 直也、高橋 雅英
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] 移動するがん細胞集団内における多様性の確立機構 (2013)
  • Author(s): 加藤 琢哉、榎本 篤、浅井 直也、村雲 芳樹、高橋 雅英
  • Organizer: 日本病理学会総会
  • Place of Presentation: ロイトン札幌、札幌