Development of a technique for identifying drug-dependent interacting proteins using cell-free based human protein arrays.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03218
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Ehime University
• Principal Investigator: Sawasaki Tatsuya 愛媛大学, プロテオサイエンスセンター, 教授 (50314969)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: サリドマイド / 無細胞 / タンパク質分解 / ユビキチン / プロテインアレイ / E3リガーゼ / 薬剤 / 副作用

Outline of Final Research Achievements

In recent years, protein degraders, represented by thalidomide and its derivatives, have been discovered in which drugs bind to the target E3 ubiquitin ligase, altering its binding specificity to the substrate protein and inducing degradation of specific proteins in a drug-dependent manner. Using protein arrays, this study succeeded in developing the world's first cell-free technique to comprehensively identify proteins that interact in a drug-dependent manner in vitro. Thalidomide has caused a worldwide drug-related harm in that fetuses with abnormal limb development were born as a result of pregnant women taking the drug. In this study, we used the protein array technology developed above and found that the degradation of PLZF by thalidomide induces teratogenicity.

Free Research Field

蛋白質科学

Academic Significance and Societal Importance of the Research Achievements

サリドマイドによる世界規模の薬害をもたらしたにも関わらず、現在、サリドマイド誘導体は多発性骨髄腫のキラードラッグとなり、多くの患者で利用されている。本研究により、その薬害メカニズムを明らかにすることができた。さらに本研究は、ヒトプロテインアレイを用いた薬の副作用を解明する手法の構築であったことから、今後、本手法が広く使われ、薬の副作用の解明に向けた方法論を提示したことになり、本研究成果は学術的にも社会的にも大きな意義を持っているといえる。