The alpha1-6-fucosyltransferase gene and its biological significance.
GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1-6-fucosyltransferase (alpha1-6FucT) catalyzes the transfer of fucose from GDP-Fuc to N-linked type complex glycoproteins. This enzyme was purified from a human fibroblast cell line, porcine brain, a human gastric cancer cell line and human blood platelets. cDNA cloning of porcine and human alpha1-6FucT was performed from a porcine brain and gastric cancer cell cDNA libraries, respectively. Their homology is 92.2% at the nucleotide level and 95.7% at the amino acid level. No putative N-glycosylation sites were found in the predicted amino acid sequence. No homology to other fucosyltransferases such as alpha1-2FucT, alpha1-3FucT and alpha1-4FucT was found except for a region consisting of nine amino acids. The alpha1-6FucT gene is located at chromosome 14q24.3, which is also a different location from other fucosyltransferases reported to date. The alpha1-6FucT gene is the oldest gene family in the phylogenic trees among the nine cloned fucosyltransferase genes. alpha1-6FucT is widely expressed in various rat tissues and the expression of alpha1-6FucT in the liver is enhanced during hepatocarcinogenesis of LEC rats which develop hereditary hepatitis and hepatomas. In cases of human liver diseases, alpha1-6FucT is expressed in both hepatoma tissues and their surrounding tissues with chronic liver disease, but not in the case of normal liver. Serum alpha1-6-fucosylated alpha-fetoprotein (AFP) has been employed for an early diagnosis of patients with hepatoma. The mechanisms by which alpha1-6 fucosylation of AFP occurs in the hepatoma is not due to the up-regulation of alpha1-6FucT alone. Interestingly, when the alpha1-6FucT gene is transfected into Hep3B, a human hepatoma cell line, tumor formation in the liver of nude mice after splenic injection is dramatically suppressed. In this review, we focus on alpha1-6FucT and summarize its properties, gene expression and biological significance.
Miyoshi
E
E
Department of Biochemistry, Osaka University Medical School, Room B-1, 2-2 Yamadaoka, Suita, Osaka, Japan.
Noda
K
K
Yamaguchi
Y
Y
Inoue
S
S
Ikeda
Y
Y
Wang
W
W
Ko
J H
JH
Uozumi
N
N
Li
W
W
Taniguchi
N
N
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D005647:Fucosyltransferases / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D020318:Rats, Long-Evans; D013552:Swine; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism
D018076:DNA, Complementary; D000509:alpha-Fetoproteins; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase