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The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate
Open accessAbstract
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.
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Citations
Cited by
Functions of Cell Surface Heparan Sulfate Proteoglycans
Bernfield, M., Götte, M., Park, P. W., Reizes, O., Fitzgerald, M. L., Lincecum, J., & Zako, M. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.729 · Cited by 2,688
Synthesis and sorting of proteoglycans
Prydz, K., & Dalen, K. T. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.2.193 · Cited by 481
Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1-Deficient Mice
Lin, X., Wei, G., Shi, Z., Dryer, L., Esko, J. D., Wells, D. E., & Matzuk, M. M. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9798 · Cited by 427
Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions
Tumova, S., Woods, A., & Couchman, J. R. (2000) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(99)00116-8 · Cited by 375
Marquardt, T., & Denecke, J. (2003) · European Journal of Pediatrics · doi:10.1007/s00431-002-1136-0 · Cited by 290
Metadata
- Authors
- Lind, T., Tufaro, F., McCormick, C., Lindahl, U., & Lidholt, K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 273
- Issue
- 41
- Pages
- 26265-26268
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2047649254
- Cited by
- 429
- References
- 0
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate. https://app.cochat.ai/papers/10.1074/jbc.273.41.26265
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- Lind, T., Tufaro, F., McCormick, C., Lindahl, U., & Lidholt, K. (1998). The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.41.26265
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
