Analysis of ubiquitin network regulation by TRIM family proteins

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02607
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Hokkaido University
• Principal Investigator: Hatakeyama Shigetsugu 北海道大学, 医学研究院, 教授 (70294973)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ユビキチン / TRIMタンパク質 / 細胞内シグナル

Outline of Final Research Achievements

It has been reported that TRIM family ubiquitin ligases are involved in the regulation of signal transduction and autophagy that control immune response, oncogenesis and cell differentiation, and has recently attracted attention in many fields of intracellular signal transduction system. In this application, we comprehensively analyzed the intracellular network system based on TRIM family ubiquitin ligase by comprehensive knockdown screening and proteomics method specialized in ubiquitination. Furthermore, by elucidating the functions of TRIM family in oncogenesis and the immune system, we proceeded to obtain findings that contribute to the diagnosis and treatment of autoimmune diseases, allergic diseases and cancers.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

これまでは各TRIMタンパク質の機能が個別に報告されてきたが、本申請研究では網羅的にTRIMタンパク質が関するさまざまな細胞内シグナルを解析し、新たな基質タンパク質の同定に結び付いた。本研究成果により、TRIMファミリーによる翻訳後修飾（特にユビキチン化）の生理機能および疾患との関連の解明が進み、最終的にはがん化、細胞分化・個体発生・神経変性疾患・自己免疫疾患などの多様な方面おける総合的理解にも貢献する可能性が高い。