Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K
Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 575, S-751 23 Uppsala, Sweden.
J Biol Chem. 1998 Oct 9;273(41):26265-8. doi: 10.1074/jbc.273.41.26265.
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.
遗传性多发性骨软骨瘤以多发性软骨肿瘤为特征，归因于三个不同位点（记为EXT1 - 3）的突变。在此，我们报告了从牛血清中纯化出一种蛋白质，它具有糖胺聚糖硫酸乙酰肝素（HS）生物合成所需的D - 葡糖醛酸（GlcA）和N - 乙酰 - D - 葡糖胺（GlcNAc）转移酶活性。该蛋白质被鉴定为EXT2。EXT2的表达产生了一种具有两种糖基转移酶活性的蛋白质。此外，先前发现能挽救缺陷性HS生物合成的EXT1（麦考密克，C.，勒迪克，Y.，马丁代尔，D.，马蒂森，K.，埃斯福德，L. E.，戴尔，A. P.，和图法罗，F.（1998年）《自然遗传学》19卷，第158 - 161页），被证明能提高突变细胞中低水平的GlcA和GlcNAc转移酶。因此，肿瘤抑制因子EXT家族的至少两个成员编码参与HS生物合成链延长步骤的糖基转移酶。
