Mar 21, 2001

The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis

EMBO Reports
C SenayMarion Kusche-Gullberg

Abstract

The D-glucuronyltransferase and N-acetyl-D-glucosaminyltransferase reactions in heparan sulfate biosynthesis have been associated with two genes, EXT1 and EXT2, which are also implicated in the inherited bone disorder, multiple exostoses. Since the cell systems used to express recombinant EXT proteins synthesize endogenous heparan sulfate, and the EXT proteins tend to associate, it has not been possible to define the functional roles of the individual protein species. We therefore expressed EXT1 and EXT2 in yeast, which does not synthesize heparan sulfate. The recombinant EXT1 and EXT2 were both found to catalyze both glycosyltransferase reactions in vitro. Coexpression of the two proteins, but not mixing of separately expressed recombinant EXT1 and EXT2, yields hetero-oligomeric complexes in yeast and mammalian cells, with augmented glycosyltransferase activities. This stimulation does not depend on the membrane-bound state of the proteins.

Mentioned in this Paper

Transformation, Genetic
Precipitin Tests
Tumor Suppressor Genes
EXT1
Metastasis Suppressor Genes
Hereditary Multiple Exostoses
Complex (molecular entity)
Proteins, Recombinant DNA
Glucuronosyltransferase
COS-7 Cells

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