Identification and fuctional analysis of a novel molecular signal network related to NF1 tumorigenesis via the activation of translation mediated by TCTP

• Project/Area Number: 16K07118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Niigata University (2019); Kumamoto University (2016-2018)
• Principal Investigator: Kobayashi Daiki 新潟大学, 医歯学系, 助教 (20448517)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NF1 / TCTP / 悪性腫瘍 / EF1A2 / 翻訳伸長因子 / 神経線維腫症１型 / 神経線維腫症１型腫瘍 / タンパク質翻訳

Outline of Final Research Achievements

In order to elucidate the pathogenesis of neurofibromatosis type 1 (NF1), we investigated the role of TCTP-mediated translational control mechanism in NF1 tumor cells. TCTP significantly binds to the translation elongation factor complex, and in particular, TCTP forms a complex with the translation elongation factors including EF1A2, which promotes protein translation in NF1 tumor cells. Therefore, This study demonatrates that TCTP promotes the pathogenesis of NF1 tumor by activating the protein translation elongation by interacting with EF1A2.

Academic Significance and Societal Importance of the Research Achievements

神経線維腫症１型（NF1）は悪性腫瘍を含む多彩な病態を示す遺伝性疾患である。NF1の詳細な分子機序や病態マーカーおよび治療標的は報告されておらず、治療法は対処療法のみである。本研究により、TCTPを介した翻訳制御機構が明らかとなり、NF1腫瘍の病態を進行させていることが考えられ、その機能阻害がNF1腫瘍の治療標的として有効であることが示唆された。

Research Products

• [Journal Article] Identification of a Specific Translational Machinery via TCTP-EF1A2 Interaction Regulating NF1-associated Tumor Growth by Affinity Purification and Data-independent Mass Spectrometry Acquisition (AP-DIA) (2019)
  • Author(s): Kobayashi Daiki, Tokuda Takaho, Sato Kyosuke, Okanishi Hiroki, Nagayama Megumi, Hirayama-Kurogi Mio, Ohtsuki Sumio, Araki Norie
  • Journal Title: Molecular & Cellular Proteomics Volume: 18 Issue: 2 Pages: 245-262
  • DOI: 10.1074/mcp.ra118.001014
  • Peer Reviewed / Open Access
• [Journal Article] Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency (2018)
  • Author(s): Ito Naofumi、Katoh Kaoru、Kushige Hiroko、Saito Yutaka、Umemoto Terumasa、Matsuzaki Yu、Kiyonari Hiroshi、Kobayashi Daiki、Soga Minami、Era Takumi、Araki Norie、Furuta Yasuhide、Suda Toshio、Kida Yasuyuki、Ohta Kunimasa
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1634-1634
  • DOI: 10.1038/s41598-018-20057-1
  • Peer Reviewed / Open Access
• [Journal Article] jPOSTrepo: an international standard data repository for proteomes. (2017)
  • Author(s): Okuda S, Watanabe Y, Moriya Y, Kawano S, Yamamoto T, Matsumoto M, Takami T, Kobayashi D, Araki N, Yoshizawa AC, Tabata T, Sugiyama N, Goto S, Ishihama Y.
  • Journal Title: Nucleic Acids Res. Volume: 45 Issue: D1 Pages: D1107-D1111
  • DOI: 10.1093/nar/gkw1080
  • NAID: 120006353864
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] プロテオミクスデータの細胞生物学的な検証法 (2016)
  • Author(s): Kobayashi D, Araki N.
  • Journal Title: Proteome Letters Volume: 1 Pages: 37-43
  • NAID: 130007498972
  • Peer Reviewed / Open Access
• [Presentation] インフォマティクスに支えられるプロテオーム解析 (2019)
  • Author(s): 小林 大樹 , 荒木 令江
  • Organizer: 日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会
  • Invited
• [Presentation] クロスリンキング質量分析（XL-MS）によるNF1関連病態因子TCTPと翻訳伸長因子群 の相互作用形式の解明 (2019)
  • Author(s): 椋木 浩太, 小林 大樹, 徳田 高穂, 荒木 令江
  • Organizer: 日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会
• [Presentation] Analysis of the interaction between NF1-associated factor TCTP and translation elongation factors by cross-linking mass spectrometry coupled with affinity purification (2019)
  • Author(s): Daiki Kobayashi, Kota Mukugi, Takaho Tokuda, Norie Araki
  • Organizer: 2019 HUPO World Congress
  • Int'l Joint Research
• [Presentation] SWATH定量による NF1関連因子TCTP２量体型と翻訳伸長因子群の相互作用解析 (2018)
  • Author(s): 小林大樹、徳田高穂、岡西 広樹、荒木 令江
  • Organizer: 日本質量分析学会・日本プロテオーム学会2018年合同大会（MSP2018）
• [Presentation] 質量分析によるプロテオーム解析 (2018)
  • Author(s): 小林大樹
  • Organizer: 第2回・質量分析インフォマティクス・ハッカソン・シンポジウム
  • Invited
• [Presentation] TCTP-EF1A2-翻訳伸長因子複合体を介した神経線維腫症1型腫瘍特異的な翻訳機構の解析 (2017)
  • Author(s): 小林大樹、徳田高穂、岡西 広樹、大槻 純男、荒木 令江
  • Organizer: 2017年度生命科学系学会合同年次大会（Conbio2017）
• [Presentation] 質量分析・プロテオーム (2017)
  • Author(s): 小林大樹
  • Organizer: 第1回・質量分析インフォマティクス・ハッカソン
  • Invited
• [Presentation] Identification of TCTP-EF1A2-mediated translation machinery regulating NF1-associated tumor growth by affinity purification and data-independent acquisition. (2017)
  • Author(s): Daiki Kobayashi, Takaho Tokuda, Hiroki Okanishi, Megumi Nagayama, Sumio Ohtsuki, Norie Araki
  • Organizer: HUPO2017 (16th HUPO World Congress)
  • Int'l Joint Research
• [Presentation] プロテオームデータにある生物学的な重要性を見出すための“Computational”ツール (2017)
  • Author(s): 小林大樹、荒木令江
  • Organizer: 日本プロテオーム学会2017年会 (JHUPO2017)
  • Invited
• [Presentation] マルチオミクス解析（融合プロテオミクス：マルチオミクス解析とデータマイニングの標準化を目指して） (2017)
  • Author(s): 小林大樹
  • Organizer: 第44回BMSコンファレンス（BMS2017）
  • Invited
• [Presentation] Interactome analysis identified a novel binding manner of TCTP-translation elongation factors in Neurofibromatosis type 1 (NF1)-associated tumors. (2016)
  • Author(s): Daiki Kobayashi, Takaho Tokuda, Megumi Nagayama, Kyosuke Sato, Mio Hirayama, Sumio Ohtsuki, Norie Araki
  • Organizer: AOHUPO2016
  • Place of Presentation: Fleur De Chine Hotel, Sun Moon Lake, Nantou, Taiwan
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] Interactome analysis identified the specific interaction of TCTP and EF1A2 in Neurofibromatosis type 1 (NF1)-associated tumors (2016)
  • Author(s): Daiki Kobayashi, Takaho Tokuda, Megumi Nagayama, Kyosuke Sato, Sumio Ohtsuki, Norie Araki
  • Organizer: HUPO2016
  • Place of Presentation: Taipei International Convention Center, Taipei, Taiwan
  • Year and Date: 2016-09-18
  • Int'l Joint Research
• [Presentation] Interactome解析によるNF1腫瘍内のTCTP－翻訳伸長因子複合体の機能解明 (2016)
  • Author(s): 小林大樹、徳田高穂、長山慈、佐藤恭介、平山未央、大槻純男、荒木令江
  • Organizer: 日本プロテオーム学会2016年大会（JHUPO第14回大会）
  • Place of Presentation: 北里大学薬学部 白金キャンパス (東京都港区）
  • Year and Date: 2016-07-28