Elucidation of intracellular ubiquitin chains formation mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22726
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Hoshi University
• Principal Investigator: Soma Ai (海保愛) 星薬科大学, 先端生命科学研究所, 特任助教 (60420684)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: ユビキチン / プロテアソーム / タンパク質分解 / ユビキチンリガーゼ

Outline of Final Research Achievements

The ubiquitin proteasome system regulates numerous biological pathways through target specific protein degradation and is indispensable for maintaining cellular proteostasis. Ubiquitin monomers assemble into poly-ubiquitin chains with different linkage topologies by conjugating with each other through one of seven lysine residues or the first methionine of the ubiquitin molecule. Such diversity in the form of ubiquitin chains is the basis for the functional diversity of protein ubiquitylation: the concept known as the ubiquitin code. However, it is largely unknown how complex poly-ubiquitin architectures are efficiently generated in cells. In this study, we analyzed ubiquitin chain elongation factors and identified proteins co-localized with proteasomes and ubiquitin chaperons. In addition, we used a proteomics approach to find target proteins regulated by ubiquitin chain elongation factors.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ユビキチン・プロテアソーム系による選択的なタンパク質分解は様々な生命機能を制御しており、その破綻はがんや神経変性疾患、免疫疾患など、多様な病態に関わることが知られている。本研究で解明したタンパク質分解の分子機構は将来的にこれら疾患の理解につながることが期待される。