PMID- 24895123 OWN - NLM STAT- MEDLINE DCOM- 20150211 LR - 20221207 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 30 DP - 2014 Jul 25 TI - An oncogenic protein Golgi phosphoprotein 3 up-regulates cell migration via sialylation. PG - 20694-705 AB - 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. FAU - Isaji, Tomoya AU - Isaji T FAU - Im, Sanghun AU - Im S FAU - Gu, Wei AU - Gu W FAU - Wang, Yuqin AU - Wang Y FAU - Hang, Qinglei AU - Hang Q FAU - Lu, Jishun AU - Lu J FAU - Fukuda, Tomohiko AU - Fukuda T FAU - Hashii, Noritaka AU - Hashii N FAU - Takakura, Daisuke AU - Takakura D FAU - Kawasaki, Nana AU - Kawasaki N FAU - Miyoshi, Hiroyuki AU - Miyoshi H FAU - Gu, Jianguo AU - Gu J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (GOLPH3 protein, human) RN - 0 (Membrane Proteins) RN - 0 (Phosphoproteins) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.4.99.- (Sialyltransferases) RN - GZP2782OP0 (N-Acetylneuraminic Acid) RN - EC 2.4.99.1 (beta-D-Galactoside alpha 2-6-Sialyltransferase) SB - IM MH - Cell Movement/*physiology MH - Gene Knockdown Techniques MH - Glycosylation MH - HeLa Cells MH - Humans MH - Membrane Proteins/genetics/*metabolism MH - N-Acetylneuraminic Acid/genetics/*metabolism MH - Phosphoproteins/genetics/*metabolism MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Sialyltransferases/genetics/metabolism MH - Signal Transduction/*physiology MH - beta-D-Galactoside alpha 2-6-Sialyltransferase PMC - PMC4110280 EDAT- 2014/06/05 06:00 MHDA- 2015/02/12 06:00 PMCR- 2015/07/25 CRDT- 2014/06/05 06:00 PHST- 2014/06/05 06:00 [entrez] PHST- 2014/06/05 06:00 [pubmed] PHST- 2015/02/12 06:00 [medline] PHST- 2015/07/25 00:00 [pmc-release] AID - S0021-9258(20)47590-8 [pii] AID - M113.542688 [pii] AID - 10.1074/jbc.M113.542688 [doi] PST - ppublish SO - J Biol Chem. 2014 Jul 25;289(30):20694-705. doi: 10.1074/jbc.M113.542688.