Human Molecular Genetics, Vol 8, 2155-2164, Copyright © 1999 by Oxford University Press
AD Simmons, MM Musy, CS Lopes, LY Hwang, YP Yang and M Lovett
Hereditary multiple exostoses (HME) is an autosomal dominant condition in
which bony outgrowths occur from the juxtaepiphyseal regions of the long
bones. In a few percent of cases these exostoses undergo malignant
transformation to chondrosarcomas. HME results from mutations in one of two
homologous genes, EXT1 and EXT2. These are members of a new gene family
that is conserved from Caenorhabditis elegans to higher vertebrates. In
humans this family comprises five genes which are most conserved at their
C-termini, but they do not contain any discernible functional motifs and
their function(s) is unclear. Indirect evidence suggests that EXT proteins
are involved in glycosaminoglycan synthesis, act as tumor suppressors and
affect hedgehog signaling. One recent study has also reported that these
proteins co-purify with glycosyltransferase (GlcA and GlcNAc transferase)
activity and on that basis it has been postulated that they are themselves
glycosyl- transferases. We performed two-hybrid screens with a fragment of
EXT2 from the region that is most highly conserved in the gene family and
identified two interacting proteins: the tumor necrosis factor type 1
asso-ciated protein and a novel UDP-GalNAc:poly-peptide N -
acetylgalactosaminyltransferase. Significantly, both these interactions
were abrogated by a disease-causing EXT mutation, indicating that they are
important in the etiology of HME. The EXT2-GalNAc-T5 interaction provides
the first direct physical link between EXT proteins and known components of
glycosamino-glycan synthesis.
ARTICLES
A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses
The McDermott Center and
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Leskovar, H. Wegele, N. D. Werbeck, J. Buchner, and J. Reinstein The ATPase Cycle of the Mitochondrial Hsp90 Analog Trap1 J. Biol. Chem., April 25, 2008; 283(17): 11677 - 11688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Lemos, P. Kotanko, P. T. Christie, B. Harding, T. Javor, C. Smith, R. Eastell, and R. V. Thakker A Novel EXT1 Splice Site Mutation in a Kindred with Hereditary Multiple Exostosis and Osteoporosis J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5386 - 5392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Morita, A. Amagai, and Y. Maeda Translocation of the Dictyostelium TRAP1 homologue to mitochondria induces a novel prestarvation response J. Cell Sci., November 15, 2004; 117(24): 5759 - 5770. [Abstract] [Full Text] [PDF]
|
|