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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: RNA結合タンパク / 転写後制御 / PD-L1 / RNA結合タンパク質 / 3'-UTR / 転写後調節 / 免疫 / 発現制御 / 癌

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.

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。

Research Products

• [Presentation] Novel mechanism of post-transcriptional regulation of PD-L1 expression by 3’-UTR binding proteins. / 3´-UTR結合タンパクによるPD-L1発現の転写後調節機構の解明 (2017)
  • Author(s): Yasunori Kogure, Keisuke Kataoka, Yosaku Watatani, Ayana Kon, Kenichi Yoshida, Masahiro Nakagawa, Seishi Ogawa
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Novel mechanism of post-transcriptional regulation of PD-L1 expression by 3’-UTR binding proteins. / 3´-UTR結合タンパクによるPD-L1発現の転写後調節機構の解明 (2017)
  • Author(s): Yasunori Kogure, Keisuke Kataoka, Shungo Adachi, Yosaku Watatani, Ayana Kon, Kenichi Yoshida, Masahiro Nakagawa, Tomohisa Hatta, Tohru Natsume, Seishi Ogawa,
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Novel Mechanism of Post-Transcriptional Regulation of PD-L1 Expression By 3’-UTR Binding Proteins (2017)
  • Author(s): Yasunori Kogure, Keisuke Kataoka, Shungo Adachi, Yosaku Watatani, Ayana Kon, Kenichi Yoshida, Masahiro Nakagawa, Tomohisa Hatta, Tohru Natsume and Seishi Ogawa
  • Organizer: the 59th ASH Annual Meeting
  • Int'l Joint Research