rib-2, a Caenorhabditis elegansHomolog of the Human Tumor Suppressor EXT Genes Encodes a Novel α1,4-N-Acetylglucosaminyltransferase Involved in the Biosynthetic Initiation and Elongation of Heparan…

By H. Kitagawa, Noriyuki Egusa, J. Tamura, M. Kusche‐Gullberg, U. Lindahl, K. Sugahara. 2001

57 citations recorded by the source corpus.

The proteins encoded by the EXT1,EXT2, and EXTL2 genes, members of the hereditary multiple exostoses gene family of tumor suppressors, are glycosyltransferases required for the heparan sulfate biosynthesis. Only two homologous genes, rib-1 and rib-2, of the mammalian EXT genes were identified in theCaenorhabditis elegans genome. Although heparan sulfate is found in C. elegans, the involvement of the rib-1 and rib-2 proteins in heparan sulfate biosynthesis remains unclear. In the present study, the substrate specificity of a soluble recombinant form of the rib-2 protein was determined and compared with those of the recombinant forms of the mammalian EXT1, EXT2, and EXTL2 proteins. The present findings revealed that the rib-2 protein was a unique α1,4-N-acetylglucosaminyltransferase involved in the biosynthetic initiation and elongation of heparan sulfate. In contrast, the findings confirmed the previous observations that both the EXT1 and EXT2 proteins were heparan sulfate copolymerases with both α1,4-N-acetylglucosaminyltransferase and β1,4-glucuronyltransferase activities, which are involved only in the elongation step of the heparan sulfate chain, and that the EXTL2 protein was an α1,4-N-acetylglucosaminyltransferase involved only in the initiation of heparan sulfate synthesis. These findings suggest that the biosynthetic mechanism of heparan sulfate inC. elegans is distinct from that reported for the mammalian system.

Subfields: Cell Biology, Hepatology, Molecular Biology

Citations in the corpus