Oncogene database

64083

GOLPH3

golgi phosphoprotein 3 (coat-protein);GOLPH3;golgi phosphoprotein 3 (coat-protein)

Golgi phosphoprotein 3|coat protein GPP34|coat-protein|golgi peripheral membrane protein 1, 34 kDa|golgi protein|golgi-associated protein|mitochondrial DNA absence factor

5p13.3

protein-coding

Recently, the Golgi phosphoprotein 3 (GOLPH3) and its yeast homolog Vps74p have been characterized as essential for the Golgi localization of glycosyltransferase in yeast. GOLPH3 has been identified as a new oncogene that is commonly amplified in human cancers to modulate mammalian target of rapamycin signaling. However, the molecular mechanisms of the carcinogenic signaling pathway remain largely unclear. To investigate whether the expression of GOLPH3 was involved in the glycosylation processes in mammalian cells, and whether it affected cell behavior, we performed a loss-of-function study. Cell migration was suppressed in GOLPH3 knockdown (KD) cells, and the suppression was restored by a re-introduction of the GOLPH3 gene. HPLC and LC/MS analysis showed that the sialylation of N-glycans was specifically decreased in KD cells. The specific interaction between sialyltransferases and GOLPH3 was important for the sialylation. Furthermore, overexpression of alpha2,6-sialyltransferase-I rescued cell migration and cellular signaling, both of which were blocked in GOLPH3 knockdown cells. These results are the first direct demonstration of the role of GOLPH3 in N-glycosylation to regulate cell biological functions.

Cytokinesis is an intricate process that requires an intimate interplay between actomyosin ring constriction and plasma membrane remodelling at the cleavage furrow. However, the molecular mechanisms involved in coupling the cytoskeleton dynamics with vesicle trafficking during cytokinesis are poorly understood. The highly conserved Golgi phosphoprotein 3 (GOLPH3), functions as a phosphatidylinositol 4-phosphate (PI4P) effector at the Golgi. Recent studies have suggested that GOLPH3 is up-regulated in several cancers and is associated with poor prognosis and more aggressive tumours. In Drosophila melanogaster, GOLPH3 localizes at the cleavage furrow of dividing cells, is required for successful cytokinesis and acts as a key molecule in coupling phosphoinositide (PI) signalling with actomyosin ring dynamics. Because cytokinesis failures have been linked with pre-malignant disease and cancer, the novel connection between GOLPH3 and cytokinesis imposes new fields of investigation in cancer biology and therapy.

The highly conserved Golgi phosphoprotein 3 (GOLPH3) protein, a component of Trans-Golgi Network (TGN), has been defined as a "first-in-class Golgi oncoprotein" and characterized as a Phosphatidylinositol 4-phosphate [PI(4)P] effector at the Golgi. GOLPH3 is commonly amplified in several solid tumors. Furthermore this protein has been associated with poor prognosis in many cancers. Highly conserved from yeast to humans, GOLPH3 provides an essential function in vesicle trafficking and Golgi structure. Recent data have also implicated this oncoprotein in regulation of cytokinesis, modulation of mitochondrial mass and cellular response to DNA damage. A minute dissection of the molecular pathways that require GOLPH3 protein will be helpful to develop new therapeutic cancer strategies.