Role of the ubiquitin system in the regulation of gene expression

• Project Area: New aspect of the ubiquitin system : its enormous roles in protein regulation
• Project/Area Number: 24112004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Metropolitan Institute of Medical Science (2016); National Institute of Health Sciences (2012-2015)
• Principal Investigator: OHTAKE Fumiaki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (60447373)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥95,810,000 (Direct Cost: ¥73,700,000、Indirect Cost: ¥22,110,000); Fiscal Year 2016: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2015: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2014: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2013: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2012: ¥27,950,000 (Direct Cost: ¥21,500,000、Indirect Cost: ¥6,450,000)
• Keywords: ユビキチン / 翻訳後修飾 / 蛋白質 / 発現制御

Outline of Final Research Achievements

Ubiquitination is an essential post-translational modification (PTM) with diverse functions. In this study, we showed that ubiquitin, itself a PTM, is functionally regulated by acetylation. We identified histone H2B as a substrate of acetyl-ubiquitylation. Moreover, we established a strategy for quantifying K48/K63 branched ubiquitin chains, and found a cellular role of the branched ubiquitin chains.

Research Products

• [Journal Article] The K48-K63 branched ubiquitin chain regulates NF-kappaB signaling (2016)
  • Author(s): Ohtake F, Saeki Y, Ishido S, Kanno J, Tanaka K
  • Journal Title: Mol. Cell Volume: 64 Issue: 2 Pages: 251-266
  • DOI: 10.1016/j.molcel.2016.09.014
  • Peer Reviewed
• [Journal Article] The complexity of ubiquitin architecture. (2016)
  • Author(s): Ohtake, F., and Tsuchiya, H
  • Journal Title: J Biochem Volume: 161 Pages: 125-133
  • DOI: 10.1093/jb/mvw088
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ubiquitin acetylation inhibits polyubiquitin chain elongation. (2015)
  • Author(s): Ohtake F, Saeki Y, Sakamoto K, Ohtake K, Nishikawa H, Tsuchiya H, Ohta T, Tanaka K, Kanno J.
  • Journal Title: EMBO Rep. Volume: 16 Issue: 2 Pages: 192-201
  • DOI: 10.15252/embr.201439152
  • Peer Reviewed / Open Access
• [Presentation] Cellular function of the Lys48/Lys63 branched ubiquitin chain (2016)
  • Author(s): Ohtake F
  • Organizer: 国際シンポジウム「Diverse functions of Ubiquitin : Degradation, Signaling, and Beyond」
  • Place of Presentation: 京都大学（京都府京都市）
  • Int'l Joint Research / Invited
• [Presentation] Quantitative analysis of the branched ubiquitin chains (2016)
  • Author(s): Ohtake F, Saeki Y, Tanaka K
  • Organizer: 第39回日本分子生物学会シンポジウム
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Invited
• [Presentation] Ubiquitin acetylation regulates polyubiquitin chain elongation (2016)
  • Author(s): Ohtake F, Saeki Y, Tanaka K
  • Organizer: FASEB Conference‘Ubiquitin and cellular regulation’
  • Place of Presentation: Big Sky、米国
  • Int'l Joint Research
• [Presentation] ERαはUBE3CのユビキチンE3リガーゼ活性に対するリガンド依存的な調整因子として機能する (2015)
  • Author(s): 1.岡田麻衣子、大竹史明、西川裕之、佐伯泰、田中啓二、太田智彦.
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] ERはリガンド依存的なユビキチン化制御因子として機能する (2015)
  • Author(s): 3.岡田 麻衣子、西川 裕之、呉 文文、大竹 史明、佐伯 泰、田中啓二、太田 智彦
  • Organizer: 日本内分泌学会 第33回内分泌代謝学サマーセミナー
  • Place of Presentation: 福岡県柳川市
  • Year and Date: 2015-07-09
• [Remarks] 蛋白質代謝研究室ホームページ
  • URL: http://www.igakuken.or.jp/pro-meta/