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The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.

http://www.ncbi.nlm.nih.gov/pubmed/9756849

Hereditary multiple exostoses, characterized by multiple cartilaginous tumors, is ascribed to mutations at three distinct loci, denoted EXT1-3. Here, we report the purification of a protein from bovine serum that harbored the D-glucuronyl (GlcA) and N-acetyl-D-glucosaminyl (GlcNAc) transferase activities required for biosynthesis of the glycosaminoglycan, heparan sulfate (HS). This protein was identified as EXT2. Expression of EXT2 yielded a protein with both glycosyltransferase activities. Moreover, EXT1, previously found to rescue defective HS biosynthesis (McCormick, C., Leduc, Y., Martindale, D., Mattison, K., Esford, L. E., Dyer, A. P., and Tufaro, F. (1998) Nat. Genet. 19, 158-161), was shown to elevate the low GlcA and GlcNAc transferase levels of mutant cells. Thus at least two members of the EXT family of tumor suppressors encode glycosyltransferases involved in the chain elongation step of HS biosynthesis.

Pubmed ID: 9756849 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Bone Development | COS Cells | Cattle | Cloning, Molecular | Exostoses, Multiple Hereditary | Genes, Tumor Suppressor | Glycosyltransferases | Heparitin Sulfate | Humans | Molecular Sequence Data | N-Acetylglucosaminyltransferases | Proteins

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