RRC ID 53844
Author Isaji T, Im S, Gu W, Wang Y, Hang Q, Lu J, Fukuda T, Hashii N, Takakura D, Kawasaki N, Miyoshi H, Gu J.
Title An oncogenic protein Golgi phosphoprotein 3 up-regulates cell migration via sialylation.
Journal J. Biol. Chem.
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.
Volume 289(30)
Pages 20694-705
Published 2014-7-25
DOI 10.1074/jbc.M113.542688
PII M113.542688
PMID 24895123
PMC PMC4110280
MeSH Cell Movement / physiology* Gene Knockdown Techniques Glycosylation HeLa Cells Humans Membrane Proteins / genetics Membrane Proteins / metabolism* N-Acetylneuraminic Acid / genetics N-Acetylneuraminic Acid / metabolism* Phosphoproteins / genetics Phosphoproteins / metabolism* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Sialyltransferases / genetics Sialyltransferases / metabolism Signal Transduction / physiology*
IF 4.011
Resource
DNA material CSIV-TRE-RfA-CMV-KT (RDB12876) CS-RfA-ETBsd (RDB07917)