Glycosyltransferases regulate the expression of Golgi phosphoprotein 3 (GOLPH3)
Glycosphingolipid glycosyltransferases (GGTs) can organize as multienzyme complexes localized along the Golgi complex. However, the influence of the relative presence of GGTs on the localization of their clients is unclear. Here, we determine that expression of certain full-length GGTs increases the levels of Golgi phosphoprotein 3 (GOLPH3), an adaptor oncoprotein involved in Golgi trafficking and organization. Furthermore, we demonstrate that expression of the N-terminal domain of GGTs, which lacks the catalytic domain, is sufficient to achieve this regulation on GOLPH3 in a cell type-dependent manner. We also identify the N-terminal domain of {beta}4GalT-VI GGT as an inhibitor of GOLPH3 expression and thus a potential therapeutic application, since GOLPH3 overexpression is associated with progression and poor prognosis of multiple tumor types. Our data further suggest that the cytoplasmic tail of {beta}4GalT-VI N-terminal domain interferes with the ability of GOLPH3 to interact with phosphatidylinositol 4-phosphate, which consequently reduces the levels of GOLPH3, thereby impairing its function in the acquisition of mesenchymal features.