The roles of chondroitin-4-sulfotransferase-1 in development and disease

Abstract

The glycosaminoglycan chondroitin sulfate (CS) consists of long linear chains of repeating disaccharide units, which are covalently attached to core proteins to form CS-proteoglycans. These molecules have been shown to fulfill important biological functions in development, disease, and signaling. Biosynthesis of CS takes place in the Golgi apparatus. Concomitant to chondroitin chain elongation, sulfation of specific carbon residues by chondroitin sulfotransferase enzymes takes place. The sulfation balance and pattern of CS on specific carbon residues are tightly regulated during development, injury, and disease, with the temporal and spatial expression of chondroitin sulfotransferase genes believed to be a crucial determinant of this fine balance of chondroitin sulfation. Chondroitin-4-sulfotransferase-1 (C4ST-1)/carbohydrate sulfotransferase 11 (CHST11) is one of the enzymes involved in the sulfation of chondroitin by catalyzing the transfer of sulfate groups from a sulfate donor to the carbon-4 position of the N-acetylgalactosamine sugar of the repeating disaccharide units. Here, I summarize the significant recent advances in our understanding of the roles of C4ST-1 in vertebrate development, disease, and signaling pathways, and the transcriptional regulation of the C4ST-1 gene. Proper 4-sulfation of chondroitin by C4ST-1 plays a crucial role in the skeletal development and signaling events, and new evidence is suggestive of a potential role for C4ST-1 in human disease, including cancer.