Elucidation of the molecular mechanism of suppression of melanoma tumor formation by tyrosinase degradation-inducing compounds

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Nagasaki International University
• Principal Investigator: Fujita Hideaki 長崎国際大学, 薬学部, 教授 (80291524)
• Co-Investigator(Kenkyū-buntansha): 上田 亮太 長崎国際大学, 薬学部, 助手 (10881906) ; 藤井 佑樹 長崎国際大学, 薬学部, 准教授 (80610063)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: メラノソーム / メラニン / メラノーマ / チロシナーゼ / リソソーム / タンパク質分解 / ユビキチン / ユビキチンリガーゼ

Outline of Final Research Achievements

B16 melanoma was implanted subcutaneously into mice to form a tumor, and three types of tyrosinase degradation-inducing compounds were administered intraperitoneally to evaluate the antitumor effect, but no compounds were found that showed a significant effect. There might be unknown problems with experimental techniques. We have to discuss this matter with collaborators and resume experiments as soon as possible.
We were the first in the world to discover that membrane-bound ubiquitin ligase RNF152 is a novel pigment regulatory factor, and it was published in Membranes (IF=4.2). It was also published as the research thesis of co-experimenter Ryota Ueda, a graduate student.Together with collaborators, we continued research on the antiviral activity of ubiquitin ligase MARCH8, and the results were published in Cells (IF=6.0).

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究ではチロシナーゼ分解誘導化合物のメラノーマ治療薬への応用の可能性について検討を行った。このようなメラノーマ治療薬は、その作用機構は従来の治療薬とは異なるため、分子標的薬や免疫チェックポイント阻害薬と併用での相乗効果が期待できる。また、我々が報告した膜結合型ユビキチンリガーゼRNF152を標的としたメラニン合成調節化合物や、先述したチロシナーゼ分解誘導化合物の開発に繋がる可能性を秘めている。