Decryption of the ubiquitin code by chemo-technologies and advanced proteomics

2022 Fiscal Year Final Research Report

• Project Area: New frontier for ubiquitin biology driven by chemo-technologies
• Project/Area Number: 18H05498
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SAEKI Yasushi 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, プロジェクトリーダー (80462779)
• Co-Investigator(Kenkyū-buntansha): 大竹 史明 星薬科大学, 先端生命科学研究所, 特任准教授 (60447373)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: ユビキチン / プロテアソーム / 質量分析 / 標的タンパク質分解誘導剤 / 液－液相分離

Outline of Final Research Achievements

In this planned research, we have developed several advanced proteomics methods to analyze the ubiquitin system and strongly promoted this research project area. Major achievements include the elucidation of the ubiquitin decoders for proteasomal degradation, the discovery of the liquid-liquid phase separation of the proteasome, the development of monobodies that inhibit the ubiquitin decoder, and the discovery of new architectures of branched ubiquitin chains induced by PROTAC and its formation mechanisms. We believe that these findings will contribute to the future development of ubiquitin research and drug discovery.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

ユビキチン・プロテアソーム系を駆動するユビキチンコードとその解読分子を解明した本研究成果は、基礎科学の発展のみならず、がんや神経変性疾患など本分解経路が関与する様々な疾患の発症機構解明や近年爆発的に拡大しているユビキチン創薬の発展に大きく貢献する。