title: Overexpression of α1,6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation-independent manner.
abstract: Golgi phosphoprotein 2 (GP73) is a type II Golgi protein, which was found on examination of the fucosylated proteome as a potential tumor marker for hepatocellular carcinoma (HCC). The serum levels of both total and fucosylated GP73 were increased in the sera of patients with HCC. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and is catalyzed by α1,6-fucosyltransferase (Fut8). In the present study, we investigated the effect of Fut8 overexpression on GP73 production in the human hepatoma cell line Hep3B. The Fut8 expression vector was transfected into Hep3B cells and the expression of GP73 was investigated by Western blotting and real-time PCR. Overexpression of Fut8 dramatically enhanced the expression of GP73 at the transcriptional level. Surprisingly, this effect was not dependent on cellular fucosylation. Overexpression of a mutant Fut8, which was unable to be localized to the Golgi, did not induce GP73 production, suggesting that the localization of Fut8 in the Golgi apparatus was important for the increase in GP73 expression. This is the first demonstration of GP73 regulation through overexpression of a glycosyltransferase, which may lead to Golgi stress.
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Kenta
authors.initials: K
authors.lastname: Moriwaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Mika
authors.initials: M
authors.lastname: Terao
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamane-Ohnuki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Satoh
authors.forename: Anand S
authors.initials: AS
authors.lastname: Mehta
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D006224:Cricetinae; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D042541:Intracellular Space / Q000201:enzymology / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D016415:Sequence Alignment; D014162:Transfection
chemical_list: C410824:GOLM1 protein, human; D008565:Membrane Proteins; D005647:Fucosyltransferases