Analysis of protein sorting mechanism by a novel post-translational modification factor UBL3

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Fujita Health University
• Principal Investigator: Ageta Hiroshi 藤田医科大学, 医科学研究センター, 講師 (40416649)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: エクソソーム / UBL3 / MVB

Outline of Final Research Achievements

Exosomes derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to exosomes is not fully understood. Here, we report that ubiquitin-like 3 (UBL3) acts as a posttranslational modification (PTM) factor that regulates protein sorting to exosomes. We find that UBL3 modification is indispensable for sorting of UBL3 to MVBs and exosomes. By performing proteomics analysis, we find 1241 UBL3-interacting proteins, including Ras. We also show that UBL3 directly modifies Ras and oncogenic RasG12V mutant, and that UBL3 expression enhances sorting of RasG12V to exosomes via UBL3 modification. Collectively, these results indicate that PTM by UBL3 influences the sorting of proteins to exosomes.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

UBL3によるエクソソームへのタンパク質輸送における分子機構を明らかにすることによって、同じUBLファミリータンパク質であるユビキチンによる分解系制御機構やAtgによるオートファジー制御機構のように、新たな研究領域の展開が予見できる。エクソソームによる細胞間コミュニケーションは、疾患を含めた様々な生命現象に関与しており、特にがん転移において、非常に重要な役割を持つことが知られている。がん転移に対抗する創薬の観点においても、UBL3研究は一大分野として発展する可能性がある。