β1,4-Galactosyltransferase: Regulation and Signaling in Cancers

Abstract

It is widely known that N-linked oligosaccharides on glycoprotein are structurally altered during malignant transformation. β1,4-Galactosyltransferase (β4GalT) family is a class of enzymes responsible for the biosynthesis of N-acetyllactosamine on N-glycans by transferring UDP-galactose and consists of seven members, from β4GalT1 to β4GalT7. β4GalT5 and β4GalT6 also play a role in lactosylceramide synthesis. β4GalT family is involved in complicated protein-protein interaction networks, which link glycosylation to other cellular processes. In cancer cells, the expression of β4GalT is regulated by many factors, including transcriptional factors and also extracellular factors. Transcriptional regulation is the most critical way in β4GalT regulation. The B4GALT1 and B4GALT5 gene are both regulated by Ets1 transcription factor. EGF/RAS/ERK pathway is involved in the regulation of these genes. Exogenous reagents could regulate β4GalT by influencing the level of related transcription factors. The key procedure to determine the transcriptional factors of B4GALTs is identifying the protein associated with a particular sequence on the promoter region. Dual-Luciferase assay provides a rapid method to assess gene expression. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay are methods directly studying the interaction between transcriptional factors and target genes.