rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes encodes a novel alpha 1,4-N-acetylglucosaminyltransferase involved inthe biosynthetic initiation and elongation of heparan sulfate
H. Kitagawa et al., rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes encodes a novel alpha 1,4-N-acetylglucosaminyltransferase involved inthe biosynthetic initiation and elongation of heparan sulfate, J BIOL CHEM, 276(7), 2001, pp. 4834-4838
The proteins encoded by the EXT1, EXT2, and EXTL2 genes, members of the her
editary multiple exostoses gene family of tumor suppressors, are glycosyltr
ansferases required for the heparan sulfate biosynthesis, Only two homologo
us genes, rib-1 and rib-2, of the mammalian EXT genes were identified in th
e Caenorhabditis elegans genome. Although heparan sulfate is found in C. el
egans, the involvement of the rib-1 and rib-2 proteins in heparan sulfate b
iosynthesis remains unclear. In the present study, the substrate specificit
y of a soluble recombinant form of the rib-a protein was determined and com
pared 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 alpha1,4-N-acetylglucosaminyltransferase involved in the biosyntheti
c initiation and elongation of heparan sulfate. In contrast, the findings c
onfirmed the previous observations that both the EXT1 and EXT2 proteins wer
e heparan sulfate copolymerases with both alpha1,4-N-acetylglucosaminyltran
sferase and beta1,4-glucuronyl-transferase activities, which are involved o
nly in the elongation step of the heparan sulfate chain, and that the EXTL2
protein was an alpha1,4-N-acetylglucosaminyltransferase involved only in t
he initiation of heparan sulfate synthesis. These findings suggest that the
biosynthetic mechanism of heparan sulfate in C. elegans is distinct from t
hat reported for the mammalian system.