Development of a new radiosensitizer targeting APOBEC3G

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07734
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagasaki University
• Principal Investigator: Onodera Takae (山内貴恵) 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20535736)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: APOBEC3G / 放射線増感

Outline of Final Research Achievements

APOBEC3G was identified as a new target molecule for radiosensitization in our laboratory. In this study, a screening system using the deaminase activity of APOBEC3G as an index was constructed to evaluate the inhibitory effect of small molecules. An attempt was made to increase the throughput and optimize the screening system. However, so far compounds that inhibit the enzymatic activity of APOBEC3G have not been identified. The molecular mechanism of radiosensitization by APOBEC3G inhibition was investigated. In a particular cancer cell line, the repair process for radiation-induced DNA damage was suggested to be delayed under APOBEC3G knockdown conditions, resulting in enhanced radiosensitivity.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまでに研究代表者の所属する研究室で行われた研究結果から標的候補として見出されたAPOBEC3Gが放射線増感の標的として有効であることが、その作用機序からも示された。今後、臨床研究に展開できるAPOBEC3G阻害剤が見出せれば、放射線治療成績の向上に大きく貢献できると期待される。また、APOBEC3Gは抗HIV因子としても広く研究されており、その阻害剤はがん治療だけではなく抗HIV研究など様々な分野への貢献が期待できる。