RNF19B: A Novel E3 Ligase in the Ubiquitin Mediated Degradation of ΔF508 CFTR
George, Kathleen H.
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Cystic fibrosis is an autosomal, recessive disorder caused by mutations within the cystic fibrosis transmembrane conductance regulator, or CFTR, a chloride ion channel on the apical surface of epithelial cells. The lack of a functional CFTR leads to several issues, however, the most pressing is lung obstruction and infection caused by mucus accumulation. The most common cystic fibrosis causing mutation is ΔF508, which yields a mutant protein that is degraded prematurely in the endoplasmic-reticulum-associated degradation, or ERAD, system. In order to prevent this premature degradation, researchers have turned their attention to identifying proteins within the ERAD system that may serve as targets for drug development. Work done prior to this study has identified RNF19B, a known E3 ligase, as a potential candidate, and knockdown and overexpression of RNF19B have, respectively, increased and decreased ΔF508 CFTR in a dose-dependent manner. Immunohistochemical colocalization of RNF19B and ΔF508 CFTR has demonstrated that both proteins ER localize, suggesting the two physically interact. In this study, co-immunoprecipitation of RNF19B and ΔF508 CFTR revealed a direct protein-protein interaction, which suggests RNF19B likely acts on ΔF508 CFTR as an E3 ligase. Future studies should investigate the details of this interaction and the extent to which RNF19B is responsible for ΔF508 CFTR degradation.