Data_Sheet_1_The Autophagy Inhibitor Spautin-1 Antagonizes Rescue of Mutant CFTR Through an Autophagy-Independent and USP13-Mediated Mechanism.pdf Emanuela Pesce Elvira Sondo Loretta Ferrera Valeria Tomati Emanuela Caci Paolo Scudieri Ilaria Musante Mario Renda Nesrine Baatallah Nathalie Servel Alexandre Hinzpeter Diego di Bernardo Nicoletta Pedemonte Luis J. V. Galietta 10.3389/fphar.2018.01464.s001 https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_The_Autophagy_Inhibitor_Spautin-1_Antagonizes_Rescue_of_Mutant_CFTR_Through_an_Autophagy-Independent_and_USP13-Mediated_Mechanism_pdf/7459652 <p>The mutation F508del, responsible for a majority of cystic fibrosis cases, provokes the instability and misfolding of the CFTR chloride channel. Pharmacological recovery of F508del-CFTR may be obtained with small molecules called correctors. However, treatment with a single corrector in vivo and in vitro only leads to a partial rescue, a consequence of cell quality control systems that still detect F508del-CFTR as a defective protein causing its degradation. We tested the effect of spautin-1 on F508del-CFTR since it is an inhibitor of USP10 deubiquitinase and of autophagy, a target and a biological process that have been associated with cystic fibrosis and mutant CFTR. We found that short-term treatment of cells with spautin-1 downregulates the function and expression of F508del-CFTR despite the presence of corrector VX-809, a finding obtained in multiple cell models and assays. In contrast, spautin-1 was ineffective on wild type CFTR. Silencing and upregulation of USP13 (another target of spautin-1) but not of USP10, had opposite effects on F508del-CFTR expression/function. In contrast, modulation of autophagy with known activators or inhibitors did not affect F508del-CFTR. Our results identify spautin-1 as a novel chemical probe to investigate the molecular mechanisms that prevent full rescue of mutant CFTR.</p> 2018-12-13 04:28:53 CFTR chloride channel cystic fibrosis autophagy ubiquitination spautin-1