Development of methods for quantitative and qualitatve analyses of protein O-GlcNAcylation.

• Project/Area Number: 25650003
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: The University of Tokyo
• Principal Investigator: KUBOTA Yuji 東京大学, 医科学研究所, 助教 (70614973)
• 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: 翻訳後修飾 / シグナル伝達

Outline of Final Research Achievements

O-GlcNAcylation, a kind of protein post-translational modifications, has an important roles in various cellular functions such as cell proliferation and metabolism. Recently, it has been reported that its dysregulation causes such as diabetes and cancers. However, fundamental techniques and methods for the analysis of protein O-GlcNAcylation are insufficient. Therefore, I conducted this study for the purpose of development of new techniques in O-GlcNAc analysis.

Research Products

• [Journal Article] MCRIP1, an ERK substrate, mediates ERK-induced epigenetic gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP (2015)
  • Author(s): Kenji Ichikawa, Yuji Kubota, Takanori Nakamura, Jane S. Weng, Taichiro Tomida, Haruo Saito and Mutsuhiro Takekawa
  • Journal Title: Molecular Cell Volume: 58 Issue: 1 Pages: 35-46
  • DOI: 10.1016/j.molcel.2015.01.023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity (2015)
  • Author(s): Sato, Y., Goto, E., Shibata, Y., Kubota, Y., Yamagata, A., Goto-Ito, S., Kubota, K., Inoue, J., Takekawa, M., Tokunaga, F. and Fukai, S.
  • Journal Title: Nat. Struct. Mol. Biol. Volume: 22 Issue: 3 Pages: 222-229
  • DOI: 10.1038/nsmb.2970
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] p38とそのカスケード (2013)
  • Author(s): 久保田裕二、武川睦寛
  • Journal Title: Clinical Neuroscience Volume: 31 Pages: 657-660
• [Presentation] 癌およびRas/MAPK症候群におけるMEK変異体の異常活性化機構と抗癌剤抵抗性 (2014)
  • Author(s): 久保田裕二、武川睦寛
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜パシフィコ
  • Year and Date: 2014-11-25
• [Presentation] ERKシグナルの時空間制御異常による遺伝子発現プロファイルの変化 (2014)
  • Author(s): 久保田 裕二, 武川 睦寛
  • Organizer: 第３回修飾シグナル病若手ワークショップ
  • Place of Presentation: 神奈川県
  • Year and Date: 2014-10-01
• [Presentation] Germ-line and somatic mutations of the MEK gene modulate its kinase activity in congenital Ras-MAPK syndromes and sporadic cancers (2014)
  • Author(s): Yuji Kubota, Mutsuhiro Takekawa
  • Organizer: 第９回研究所ネットワーク国際シンポジウム
  • Place of Presentation: 大阪大学
  • Year and Date: 2014-06-20
• [Presentation] 癌および先天性Ras/MAPK症候群で認められるMEK ミスセンス変異体の異常活性化機構と疾患発症メカニズムの解明 (2014)
  • Author(s): 久保田 裕二, 武川 睦寛
  • Organizer: 日本臨床分子医学会
  • Place of Presentation: 京都市勧業館「みやこめっせ」
  • Year and Date: 2014-04-10
• [Presentation] 新規ERK基質分子MCRIP1によるERK依存的ジーンサイレンシングと上皮間葉転換の制御
  • Author(s): 市川研史、久保田裕二、Jane Weng、中村貴紀、武川睦寛
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: ウインクあいち（愛知県産業労働センター）
• [Presentation] 癌および先天性Ras/MAPK 症候群におけるMEK 遺伝子変異体の異常活性化メカニズムと疾患発症機構の解明
  • Author(s): 久保田裕二、武川睦寛
  • Organizer: 第2 回修飾シグナル病若手ワークショップ
  • Place of Presentation: 群馬県伊香保温泉
• [Presentation] 「Ras/MAPK症候群」および「孤発性癌」で認められる MEK遺伝子変異体の異常活性化機構と疾患発症メカニズムの解明
  • Author(s): 久保田裕二、木下 英司、武川睦寛
  • Organizer: 第64回日本電気泳動学会総会
  • Place of Presentation: 東北福祉大学ステーションキャンパス
• [Book] Protein Modifications in Pathogenic Dysregulation of Signaling (2015)
  • Author(s): Mutsuhiro Takekawa, Yuji Kubota
  • Total Pages: 324
  • Publisher: Springer