title: An oncogenic protein Golgi phosphoprotein 3 up-regulates cell migration via sialylation.
abstract: 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 α2,6-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.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Isaji
authors.forename: Sanghun
authors.initials: S
authors.lastname: Im
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Hang
authors.forename: Jishun
authors.initials: J
authors.lastname: Lu
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hashii
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takakura
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase