Identification and characterization of a novel Plakoglobin-binding protein highly expressed in the testes

1700020L24Rik was originally identified as one of the numerous mouse genes transcriptionally regulated by MEIOSIN (Meiosis initiator), but the function of its gene product has remained unknown. The human homolog of 1700020L24Rik is C17orf50, and both genes are highly expressed in the testes. In this study, we report that the protein encoded by 1700020L24Rik/C17orf50 is a Plakoglobin-binding protein. As its binding promotes the degradation of Plakoglobin, we named it Plakoglobin binding and degradation factor (PGBDF). PGBDF binds to the armadillo repeat of Plakoglobin via an α-helical region formed by approximately ten amino acids. PGBDF overexpression in cultured cells reduces the levels of Plakoglobin and induces cell aggregation accompanied by morphological changes. PGBDF localizes to both the cytoplasm and nucleus, and its subcellular distribution is regulated by phosphorylation. The inhibition of PGBDF phosphorylation by LiCl treatment promotes its cytoplasmic translocation, suggesting regulation by GSK3β and Wnt signaling. In mouse testes, PGBDF is predominantly expressed in interstitial regions. These findings suggest that PGBDF may contribute to the regulation of Plakoglobin levels and adhesion properties in testicular cells.