Novel mechanism of post-transcriptional regulation of PD-L1 through 3'-UTR.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15616
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kogure Yasunori 国立研究開発法人国立がん研究センター, 研究所, 研究員 (40782389)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: RNA結合タンパク / 転写後制御 / PD-L1

Outline of Final Research Achievements

The molecular mechanism by which PD-L1 is activated by disruption of PD-L1 3´-UTR has not been clarified. To this end, we focused on the regulation of PD-L1 expression by RNA-binding proteins. We have identified the functional segments within PD-L1 3´-UTR that actually regulate PD-L1 expression, and also, the RNA-binding proteins that bind to those segments were comprehensively analyzed by mass spectrometry. Some of the RNA-binding proteins that bind to these functional segments negatively affect the expression of PD-L1 expression. We are planning to investigate the molecular mechanism of these RNA binding proteins in detail.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果によりPD-L1の3´-UTRを介した転写後発現制御の詳細が明らかになり、実際に、PD-L1 3´-UTRに結合して発現を負に制御するRNA結合タンパクが複数存在していることが示された。PD-L1の新たな発現制御の仕組みが明らかになり、更にはこれらのRNA結合タンパクが創薬の標的となる可能性、あるいはPD-L1 3´-UTRの配列自体が新たな治療標的になりうる可能性があると考えられた。