Functional regulation of ubiquitin chains using chemo-technologies

2022 Fiscal Year Final Research Report

• Project Area: New frontier for ubiquitin biology driven by chemo-technologies
• Project/Area Number: 18H05499
• 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: Kyoto University
• Principal Investigator: KAZUHIRO IWAI 京都大学, 医学研究科, 教授 (60252459)
• Co-Investigator(Kenkyū-buntansha): 二木 史朗 京都大学, 化学研究所, 教授 (50199402)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: ユビキチン / ケミカルツール / 直鎖状ユビキチン鎖 / ユビキチンシグナル / がん / 自己免疫疾患

Outline of Final Research Achievements

Ubiquitin modifications express their functions when they are recognized by specific decoder molecules (UBDs). In this study, we investigated the mechanism of functional expression of linear ubiquitin chains (M1 chains) by UBD recognition using chemical tools, and the possibility of disease therapy by inhibition of the function. We demonstrated a novel mechanism of inhibition of signal transduction by M1 chains and the possibility of cancer therapy by M1 chain inhibition. In addition, the contribution of LUBAC hyperfunction to the pathogenesis of systemic lupus erythematosus was also elucidated.

Free Research Field

生化学・分子生理学

Academic Significance and Societal Importance of the Research Achievements

研究代表者はユビキチンが数珠状に連なったユビキチン鎖の1つである直鎖状ユビキチン鎖（M1鎖）を発見していた。本研究ではケミカルツールなどを用いて　M1鎖が、がん、自己免疫疾患などの疾患の発症に関わっていることを明らかにし、それらの疾患の治療に新たな道を拓いた。研究代表者は、それらの成果を所属研究機関を通して適切にプレスリリースしている。