研究活動情報｜関西学院大学

沖米田司・生命環境学部教授らが RFFL 阻害剤を同定した成果が「Biochemical Pharmacology」に掲載
Research on the RFFL inhibitor by Professor Tsukasa Okiyoneda's Team Is Published in Biochemical Pharmacology

2023.08.10

論文 Article

沖米田司・生命環境学部教授らがユビキチンリガーゼ RFFL の阻害剤を同定した成果が「Biochemical Pharmacology」に掲載されました。
　沖米田教授らの研究は、嚢胞性線維症原因タンパク質 CFTR 変異体の分解を促進するユビキチンリガーゼ RFFL の相互作用を阻害する低分子化合物を発見し、その作用機序を明らかにしたものです。今回 RFFL 阻害剤として同定した α-Tocopherol succinate はビタミン E の類縁体であり、他のビタミン E の類縁体とは異なるユニークな α-Tocopherol succinate の生物活性を説明する作用メカニズムを明らかにしました。本研究成果は、欧米で頻度が高い遺伝病である嚢胞性線維症の治療法開発につながることが期待されます。本研究は、理化学研究所、九州工業大学、北海道大学、徳島大学との共同研究により実施されました。

雑誌名：Biochemical Pharmacology（８月4日オンライン版）
論文タイトル：Identification of α-Tocopherol succinate as an RFFL-substrate interaction inhibitor inducing peripheral CFTR stabilization and apoptosis
著者：Taniguchi S, Ono Y, Doi Y, Taniguchi S, Matsuura Y, Iwasaki A, Hirata N, Fukuda R, Inoue K, Yamaguchi M, Tashiro A, Egami D, Aoki S, Kondoh Y, Honda K, Osada H, Kumeta H, Saio T, Okiyoneda T.
DOI：10.1016/j.bcp.2023.115730.

The research results of Professor Tsukasa Okiomeda of the Department of Biochemical Sciences, and his collaborators, who have identified inhibitors of the ubiquitin ligase RFFL, were published in the online edition of Biochemical Pharmacology on August 4th.
　The research of Prof. Okiyoneda and his team discovered a small molecule compound α-Tocopherol succinate that inhibits the interaction of the ubiquitin ligase RFFL with the CFTR mutant associated with cystic fibrosis. α-Tocopherol succinate, which was identified as an RFFL inhibitor in this study, is an analog of vitamin E. This research also revealed the mechanism of action of α-Tocopherol succinate, explaining its unique biological activities which are different from other vitamin E analogs. The results of this research are expected to lead to the development of treatments for cystic fibrosis, a genetic disease with high frequency in Europe and the United States. This research was conducted in collaboration with RIKEN, Kyushu Institute of Technology, Hokkaido University, and the University of Tokushima.

Journal name: Biochemical Pharmacology (August 4th online edition)
Paper title: Identification of α-Tocopherol succinate as an RFFL-substrate interaction inhibitor inducing peripheral CFTR stabilization and apoptosis
Authors: Taniguchi S, Ono Y, Doi Y, Taniguchi S, Matsuura Y, Iwasaki A, Hirata N, Fukuda R, Inoue K, Yamaguchi M, Tashiro A, Egami D, Aoki S, Kondoh Y, Honda K, Osada H, Kumeta H, Saio T, Okiyoneda T.
DOI: 10.1016/j.bcp.2023.115730.