Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu.
Heparan sulfate proteoglycans play a vital role in signaling of various growth factors in both Drosophila and vertebrates. In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG) biosynthesis. This impairs distribution and signaling activities of various morphogens such as Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Mutations in members of the exostosin (EXT) gene family lead to hereditary multiple exostosis in humans leading to bone outgrowths and tumors. In this study, we provide genetic and biochemical evidence that the human EXT1 (hEXT1) gene is conserved through species and can functionally complement the ttv mutation in Drosophila. The hEXT1 gene was able to rescue a ttv null mutant to adulthood and restore GAG biosynthesis.
Dasgupta
Ujjaini
U
Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Dixit
Bharat L
BL
Rusch
Melissa
M
Selleck
Scott
S
The
Inge
I
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006493:Heparin / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D011509:Proteoglycans / Q000096:biosynthesis; D017385:Sequence Homology; D014018:Tissue Distribution; D000099058:Exostosin 1
D029721:Drosophila Proteins; D008565:Membrane Proteins; D011509:Proteoglycans; C113073:TTV protein, Drosophila; C036090:heparin proteoglycan; D006493:Heparin; D017351:N-Acetylglucosaminyltransferases; C487133:Sotv protein, Drosophila; D000099058:Exostosin 1