Research on readthrough therapy for cystic fibrosis conducted by Professor Tsukasa Okiyoneda and Assistant Professor Yuka Kamada of the School of Biological and Environmental Sciences has been published in Cellular and Molecular Life Sciences.

Research on readthrough therapy for cystic fibrosis conducted by Professor Tsukasa Okiyoneda and Assistant Professor Yuka Kamada of the School of Biological and Environmental Sciences has been published in Cellular and Molecular Life Sciences.

In cystic fibrosis caused by nonsense mutations, translational readthrough-inducing drugs (TRIDs) can restore the production of full-length CFTR protein; however, their therapeutic efficacy remains limited because the restored protein is degraded by intracellular protein quality control mechanisms. In this study, the researchers identified the E3 ubiquitin ligase RFFL as a key factor responsible for the degradation of rescued CFTR. Furthermore, they demonstrated that suppression of RFFL significantly enhances CFTR functional recovery. These findings provide a promising new therapeutic strategy for cystic fibrosis patients carrying nonsense mutations.

Journal: Cellular and Molecular Life Sciences
Title: RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations
Authors: Hazuki Tateishi, Yukako Doi, Yuka Kamada, Tsukasa Okiyoneda
DOI: 10.1007/s00018-026-06114-3