Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants.

ABSTRACT: Pendrin (SLC26A4) is an anion exchanger abundantly expressed in the inner ear, kidney and thyroid, and its malfunction resulting from genetic mutation leads to Pendred syndrome and non‑syndromic deafness DFNB4. Pathogenic variants of the pendrin protein are less expressed than the wild‑type, but the mechanism underlying this phenomenon is unknown. In the present study, the hypothesis that reduced protein expression stems from increased protein degradation was explored. To verify this hypothesis, the protein levels and anion transport function of several pathogenic pendrin variants were measured following exposure to inhibitors of the ubiquitin‑proteasome system (UPS) and the lysosomal/autophagosomal pathways. Protein levels were measured by western blotting and quantitative imaging; ion tr

SUBMITTER: Bernardinelli E 

PROVIDER: S-EPMC11913434 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature