Extensive analyses of the LUBAC ubiquitin ligase

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H06174
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Iwai Kazuhiro 京都大学, 医学研究科, 教授 (60252459)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: ユビキチン / 炎症制御 / B細胞リンパ腫 / LUBACリガーゼ / 感染制御 / グリコーゲン代謝異常

Outline of Final Research Achievements

I conducted the functional analyses of LUBAC ubiquitin ligase, which is the only enzyme that produces the same chain as the linear ubiquitin chain discovered by the principal investigator, and its development into diseases. I elucidated the mechanism of regulation of LUBAC activity and showed that its hyperactivity can suppress immunodeficiency and autoinflammatory diseases. Furthermore, we clarified the pathogenic mechanism of lymphoma due to the enhanced function of LUBAC, the role of linear ubiquitin chains in immune system cells, and the abnormal glycogen metabolism due to HOIL-1L subunit abnormality. In addition, it has been clarified that the enhancement of LUBAC function contributes to the onset of systemic lupus erythematosus.

Free Research Field

医化学一般

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を発見していた。本研究では同ユビキチン鎖が、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た。さらに、LUBAC制御薬剤の開発に繋がる同ユビキチン鎖の生成酵素の活性調節方法を明らかにし、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。