The α1-6-fucosyltransferase gene and its biological significance

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha 1-6-fucosyltransferase (alpha 1-6FucT) 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 alpha 1-6FucT 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 alpha 1-2FucT, alpha 1-3FucT and alpha 1-4FucT was found except for a region consisting of nine amino acids. The alpha 1-GFucT gene is located at chromosome 14q24.3, which is also a different location from other fucosyltransferases reported to date. The alpha 1-GFucT gene is the oldest gene family in the phylogenic trees among the nine cloned fucosyltransferase genes. alpha 1-GFucT is widely expressed in various rat tissues and the expression of alpha 1-GFucT in the liver is enhanced during hepatocarcinogenesis of LEC rats which develop hereditary hepatitis and hepatomas. In cases of human liver diseases, alpha 1-6FucT is expressed in both hepatoma tissues and their surrounding tissues with chronic liver disease, but not in the case of normal liver. Serum alpha 1-6-fucosylated alpha-fetoprotein (AFP) has been employed for an early diagnosis of patients with hepatoma. The mechanisms by which alpha 1-6 fucosylation of AFP occurs in the hepatoma is not due to the up-regulation of alpha 1-6FucT alone. Interestingly, when the alpha 1-GFucT 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 alpha 1-6FucT and summarize its properties, gene expression and biological significance. (C) 1999 Elsevier Science B.V. All rights reserved.