Identification and functional analyses of lysine long chain fatty acylated proteins

• Project/Area Number: 16K14674
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Tokyo University of Pharmacy and Life Science (2017); Institute of Physical and Chemical Research (2016)
• Principal Investigator: Ito Akihiro 東京薬科大学, 生命科学部, 教授 (40391859)
• Co-Investigator(Renkei-kenkyūsha): Dohmae Naoshi 国立研究開発法人理化学研究所, 環境資源科学研究センター, ユニットリーダー (00321787)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ミリストイル化 / パルミトイル化 / TEAD / Hippo経路 / がん / 脂質修飾 / アシル化 / 癌 / 蛋白質 / 翻訳後修飾

Outline of Final Research Achievements

The TEAD family of transcription factors regulated by the hippo pathway is crucial for development processes and also plays roles in tumorigenesis. The transcriptional activity of TEADs is generally regulated by their co-activators YAP/TAZ. However, little is known about posttranslational modifications of TEADs. In this study, we identified TEADs as novel lysine myristoylated proteins by means of shotgun analyses using LC-MS/MS. We succeeded in generating a mouse monoclonal antibody that specifically recognizes the myristoylated from of TEADs. Using this antibody, we found that the long chain fatty acylation of lysine may be mediated by intramolecular transfer from acylated cysteine residues in TEAD proteins. In addition, we showed that the long chain fatty acylation on lysine residue is important for the binding with YAP. Our results suggest the novel regulatory mechanism of TEADs by lysine long chain fatty acylation.

Research Products

• [Presentation] リジン長鎖アシル化修飾による転写因子TEADの活性制御機構の解析 (2018)
  • Author(s): 則次 恒太、伊藤 昭博、小川 健司、鈴木 健裕、堂前 直、吉田 稔
  • Organizer: 日本農芸化学会2018年度大会
• [Presentation] 新規リジン長鎖アシル化タンパク質TEADの機能解析 (2017)
  • Author(s): 則次恒太、伊藤昭博、工藤紀雄、鈴木健裕、堂前直、吉田稔
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大学
  • Year and Date: 2017-03-17
• [Presentation] Long chain fatty acyl lysine modification of TEAD transcription factors (2017)
  • Author(s): Akihiro Ito, Kota Noritsugu, Takehiro Suzuki, Naoshi Dohmae, Minoru Yoshida
  • Organizer: FASEB Science Research Conference「Reversible Acetylation on Health and Disease (HDACs)」
  • Int'l Joint Research
• [Presentation] 転写因子TEADのリジン長鎖アシル化修飾制御機構とその機能の解析 (2017)
  • Author(s): 則次 恒太、伊藤 昭博、小川 健司、鈴木 健裕、堂前 直、吉田 稔
  • Organizer: 2017年度生命科学系学会合同年次大会