The extostosin family: Proteins with many functions

Matrix Biology

Volumn 35, Issue , 2014, Pages 25-33

  Busse Wicher, Marta ^a   Wicher, Krzysztof B ^b   Kusche Gullberg, Marion ^c  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF BERGEN   (Norway)

Author keywords

EXT1; EXT2; EXTL; Glycosyltransferase activities; Heparan sulfate

Indexed keywords

EXTL1 PROTEIN; EXTL2 PROTEIN; EXTL3 PROTEIN; EXTOSTOSIN 1; EXTOSTOSIN 2; PROTEIN; UNCLASSIFIED DRUG; EXOSTOSIN-1; GLYCOSYLTRANSFERASE; HEPARAN SULFATE; N ACETYLGLUCOSAMINYLTRANSFERASE;

AMINO ACID SEQUENCE; BIOCHEMICAL COMPOSITION; BREAST CARCINOMA; DISEASE ASSOCIATION; ENZYME ACTIVITY; HEREDITARY MULTIPLE EXOSTOSIS; HUMAN; LEUKEMIA; LOSS OF FUNCTION MUTATION; MAMMAL; MOLECULAR PATHOLOGY; MOLECULAR PHYLOGENY; MULTIPLE MYELOMA; MUTANT; NEUROBLASTOMA; NON MELANOMA SKIN CANCER; NUCLEOTIDE SEQUENCE; ORTHOLOGY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; CHEMICAL STRUCTURE; DEFICIENCY; DNA SEQUENCE; EXTRACELLULAR MATRIX; GENETICS; METABOLISM; MOLECULAR GENETICS; MULTIGENE FAMILY; PHYLOGENY; PHYSIOLOGY; POLYMERIZATION; SEQUENCE ALIGNMENT; SPECIES DIFFERENCE;

MAMMALIA;

AMINO ACID SEQUENCE; BASE SEQUENCE; EXOSTOSES, MULTIPLE HEREDITARY; EXTRACELLULAR MATRIX; GLYCOSYLTRANSFERASES; HEPARITIN SULFATE; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MULTIGENE FAMILY; N-ACETYLGLUCOSAMINYLTRANSFERASES; PHYLOGENY; POLYMERIZATION; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS, DNA; SPECIES SPECIFICITY;

EID: 84901430527     PISSN: 0945053X     EISSN: 15691802     Source Type: Journal    
DOI: 10.1016/j.matbio.2013.10.001     Document Type: Review

References (95)

1. Acquatella-Tran Van Ba I., Marchal S., Francois F., Silhol M., Lleres C., Michel B., Benyamin Y., Verdier J.M., Trousse F., Marcilhac A. Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor. J. Biol. Chem. 2012, 287:4726-4739.
2. Ahn J., Ludecke H.J., Lindow S., Horton W.A., Lee B., Wagner M.J., Horsthemke B., Wells D.E. Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat. Genet. 1995, 11:137-143.
3. Arai T., Akiyama Y., Nagasaki H., Murase N., Okabe S., Ikeuchi T., Saito K., Iwai T., Yuasa Y. EXTL3/EXTR1 alterations in colorectal cancer cell lines. Int. J. Oncol. 1999, 15:915-919.
4. Bellaiche Y., The I., Perrimon N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 1998, 394:85-88.
5. Bishop J.R., Schuksz M., Esko J.D. Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 2007, 446:1030-1037.
6. Bornemann D.J., Duncan J.E., Staatz W., Selleck S., Warrior R. Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways. Development 2004, 131:1927-1938.
7. Bornemann D.J., Park S., Phin S., Warrior R. A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo. Development 2008, 135:1039-1047.
8. Bovee J.V. EXTra hit for mouse osteochondroma. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:1813-1814.
9. Bret C., Hose D., Reme T., Sprynski A.C., Mahtouk K., Schved J.F., Quittet P., Rossi J.F., Goldschmidt H., Klein B. Expression of genes encoding for proteins involved in heparan sulphate and chondroitin sulphate chain synthesis and modification in normal and malignant plasma cells. Br. J. Haematol. 2009, 145:350-368.
10. Breton C., Bettler E., Joziasse D.H., Geremia R.A., Imberty A. Sequence-function relationships of prokaryotic and eukaryotic galactosyltransferases. J. Biochem. 1998, 123:1000-1009.
11. Bulow H.E., Hobert O. The molecular diversity of glycosaminoglycans shapes animal development. Annu. Rev. Cell Dev. Biol. 2006, 22:375-407.
12. Busse M., Kusche-Gullberg M. In vitro polymerization of heparan sulfate backbone by the EXT proteins. J. Biol. Chem. 2003, 278:41333-41337.
13. Busse M., Feta A., Presto J., Wilen M., Gronning M., Kjellen L., Kusche-Gullberg M. Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation. J. Biol. Chem. 2007, 282:32802-32810.
14. Cook A., Raskind W., Blanton S.H., Pauli R.M., Gregg R.G., Francomano C.A., Puffenberger E., Conrad E.U., Schmale G., Schellenberg G., et al. Genetic heterogeneity in families with hereditary multiple exostoses. Am. J. Hum. Genet. 1993, 53:71-79.
15. de Andrea C.E., Hogendoorn P.C. Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter. J. Pathol. 2012, 226:219-228.
16. Drake P.M., Schilling B., Niles R.K., Prakobphol A., Li B., Jung K., Cho W., Braten M., Inerowicz H.D., Williams K., et al. A lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. J. Proteome Res. 2012, 11:2508-2520.
17. Duchez S., Pascal V., Cogne N., Jayat-Vignoles C., Julien R., Cogne M. Glycotranscriptome study reveals an enzymatic switch modulating glycosaminoglycan synthesis during B-cell development and activation. Eur. J. Immunol. 2011, 41:3632-3644.
18. Esko J.D., Selleck S.B. Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu. Rev. Biochem. 2002, 71:435-471.
19. Farina A., Volinia S., Arcelli D., Francioso F., Desanctis P., Zucchini C., Pilu G., Carinci P., Morano D., Pittalis M.C., et al. Evidence of genetic underexpression in chorionic villi samples of euploid fetuses with increased nuchal translucency at 10-11weeks' gestation. Prenat. Diagn. 2006, 26:128-133.
20. Feta A., Do A.T., Rentzsch F., Technau U., Kusche-Gullberg M. Molecular analysis of heparan sulfate biosynthetic enzyme machinery and characterization of heparan sulfate structure in Nematostella vectensis. Biochem. J. 2009, 419:585-593.
21. Grobe K., Esko J.D. Regulated translation of heparan sulfate GlcNAc N-deacetylase/N- sulfotransferase isozymes by structured 5'-untranslated regions and internal ribosome entry sites. J. Biol. Chem. 2002, 277:30699-30706.
22. Gu X., Coates P.J., Boldrup L., Nylander K. p63 Contributes to cell invasion and migration in squamous cell carcinoma of the head and neck. Cancer Lett. 2008, 263:26-34.
23. Han C., Belenkaya T.Y., Khodoun M., Tauchi M., Lin X., Lin X. Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development 2004, 131:1563-1575.
24. Holmborn K., Habicher J., Kasza Z., Eriksson A.S., Filipek-Gorniok B., Gopal S., Couchman J.R., Ahlberg P.E., Wiweger M., Spillmann D., et al. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis. J. Biol. Chem. 2012, 287:33905-33916.
25. Huegel J., Sgariglia F., Enomoto-Iwamoto M., Koyama E., Dormans J.P., Pacifici M. Heparan sulfate in skeletal development, growth, and pathology: the case of hereditary multiple exostoses. Dev. Dyn. 2013, 242:1021-1032.
26. Inatani M., Irie F., Plump A.S., Tessier-Lavigne M., Yamaguchi Y. Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Science 2003, 302:1044-1046.
27. Irie F., Badie-Mahdavi H., Yamaguchi Y. Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:5052-5056.
28. Izumikawa T., Egusa N., Taniguchi F., Sugahara K., Kitagawa H. Heparan sulfate polymerization in Drosophila. J. Biol. Chem. 2006, 281:1929-1934.
29. Janot M., Audfray A., Loriol C., Germot A., Maftah A., Dupuy F. Glycogenome expression dynamics during mouse C2C12 myoblast differentiation suggests a sequential reorganization of membrane glycoconjugates. BMC Genomics 2009, 10:483.
30. Jennes I., Pedrini E., Zuntini M., Mordenti M., Balkassmi S., Asteggiano C.G., Casey B., Bakker B., Sangiorgi L., Wuyts W. Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb). Hum. Mutat. 2009, 30:1620-1627.
31. Karibe T., Fukui H., Sekikawa A., Shiratori K., Fujimori T. EXTL3 promoter methylation down-regulates EXTL3 and heparan sulphate expression in mucinous colorectal cancers. J. Pathol. 2008, 216:32-42.
32. Kim B.T., Kitagawa H., Tamura J., Saito T., Kusche-Gullberg M., Lindahl U., Sugahara K. Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode alpha 1,4-N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/heparin biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:7176-7181.
33. Kim B.T., Kitagawa H., Tamura Ji J., Kusche-Gullberg M., Lindahl U., Sugahara K. Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the essential N-acetylglucosamine transferase in the heparan sulfate biosynthesis: chain initiation and elongation. J. Biol. Chem. 2002, 277:13659-13665.
34. Kim B.T., Kitagawa H., Tanaka J., Tamura J., Sugahara K. In vitro heparan sulfate polymerization: crucial roles of core protein moieties of primer substrates in addition to the EXT1-EXT2 interaction. J. Biol. Chem. 2003, 278:41618-41623.
35. Kim S.H., Turnbull J., Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J. Endocrinol. 2011, 209:139-151.
36. Kitagawa H., Shimakawa H., Sugahara K. The tumor suppressor EXT-like gene EXTL2 encodes an a1,4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate. J. Biol. Chem. 1999, 274:13933-13937.
37. Kitagawa H., Egusa N., Tamura J.I., Kusche-Gullberg M., Lindahl U., Sugahara K. rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes encodes a novel alpha1,4-N-acetylglucosaminyltransferase involved in the biosynthetic initiation and elongation of heparan sulfate. J. Biol. Chem. 2001, 276:4834-4838.
38. Kitagawa H., Izumikawa T., Mizuguchi S., Dejima K., Nomura K.H., Egusa N., Taniguchi F., Tamura J., Gengyo-Ando K., Mitani S., et al. Expression of rib-1, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes, is indispensable for heparan sulfate synthesis and embryonic morphogenesis. J. Biol. Chem. 2007, 282:8533-8544.
39. Knudson A.J. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. U. S. A. 1971, 68:820-823.
40. Kobayashi S., Akiyama T., Nata K., Abe M., Tajima M., Shervani N.J., Unno M., Matsuno S., Sasaki H., Takasawa S., et al. Identification of a receptor for reg (regenerating gene) protein, a pancreatic beta-cell regeneration factor. J. Biol. Chem. 2000, 275:10723-10726.
41. Koziel L., Kunath M., Kelly O.G., Vortkamp A. Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev. Cell 2004, 6:801-813.
42. Kreuger J., Kjellen L. Heparan sulfate biosynthesis: regulation and variability. J. Histochem. Cytochem. 2012, 60:898-907.
43. Lai Y., Li D., Li C., Muehleisen B., Radek K.A., Park H.J., Jiang Z., Li Z., Lei H., Quan Y., et al. The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury. Immunity 2012, 37:74-84.
44. Le Merrer M., Legeai-Mallet L., Jeannin P.M., Horsthemke B., Schinzel A., Plauchu H., Toutain A., Achard F., Munnich A., Maroteaux P. A gene for hereditary multiple exostoses maps to chromosome 19p. Hum. Mol. Genet. 1994, 3:717-722.
45. Lee J.S., von der Hardt S., Rusch M.A., Stringer S.E., Stickney H.L., Talbot W.S., Geisler R., Nusslein-Volhard C., Selleck S.B., Chien C.B., et al. Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron 2004, 44:947-960.
46. Levetan C.S., Upham L.V., Deng S., Laury-Kleintop L., Kery V., Nolan R., Quinlan J., Torres C., El-Hajj R.J. Discovery of a human peptide sequence signaling islet neogenesis. Endocr. Pract. 2008, 14:1075-1083.
47. Li J.P. Heparin, heparan sulfate and heparanase in cancer: remedy for metastasis?. Anticancer Agents Med. Chem. 2008, 8:64-76.
48. Li H., Yamagata T., Mori M., Momoi M.Y. Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1. J. Hum. Genet. 2002, 47:262-265.
49. Lidholt K., Weinke J.L., Kiser C.S., Lugemwa F.N., Bame K.J., Cheifetz S., Massagué J., Lindahl U., Esko J.D. A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 1992, 89:2267-2271.
50. Lin X., Wei G., Shi Z., Dryer L., Esko J.D., Wells D.E., Matzuk M.M. Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice. Dev. Biol. 2000, 224:299-311.
51. Lind T., Lindahl U., Lidholt K. Biosynthesis of heparin/heparan sulfate. Identification of a 70-kDa protein catalyzing both the d-glucuronosyl- and the N-acetyl-d-glucosaminyltransferase reactions. J. Biol. Chem. 1993, 268:20705-20708.
52. Lind T., Tufaro F., McCormick C., Lindahl U., Lidholt K. The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. J. Biol. Chem. 1998, 273:26265-26268.
53. Lindahl U., Kusche-Gullberg M., Kjellen L. Regulated diversity of heparan sulfate. J. Biol. Chem. 1998, 273:24979-24982.
54. Liu F., Park P.J., Lai W., Maher E., Chakravarti A., Durso L., Jiang X., Yu Y., Brosius A., Thomas M., et al. A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res. 2006, 66:10815-10823.
55. Ludecke H.J., Wagner M.J., Nardmann J., La Pillo B., Parrish J.E., Willems P.J., Haan E.A., Frydman M., Hamers G.J., Wells D.E., et al. Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum. Mol. Genet. 1995, 4:31-36.
56. Mathysen D., Van Roy N., Van Hul W., Laureys G., Ambros P., Speleman F., Wuyts W. Molecular analysis of the putative tumour-suppressor gene EXTL1 in neuroblastoma patients and cell lines. Eur. J. Cancer 2004, 40:1255-1261.
57. McCormick C., Leduc Y., Martindale D., Mattison K., Esford L., Dyer A., Tufaro F. The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nat. Genet. 1998, 19:158-161.
58. McCormick C., Duncan G., Goutsos K.T., Tufaro F. The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:668-673.
59. Mitchell K.J., Pinson K.I., Kelly O.G., Brennan J., Zupicich J., Scherz P., Leighton P.A., Goodrich L.V., Lu X., Avery B.J., et al. Functional analysis of secreted and transmembrane proteins critical to mouse development. Nat. Genet. 2001, 28:241-249.
60. Mizuno K., Irie S., Sato T.A. Overexpression of EXTL3/EXTR1 enhances NF-kappaB activity induced by TNF-alpha. Cell. Signal. 2001, 13:125-130.
61. Morio H., Honda Y., Toyoda H., Nakajima M., Kurosawa H., Shirasawa T. EXT gene family member rib-2 is essential for embryonic development and heparan sulfate biosynthesis in Caenorhabditis elegans. Biochem. Biophys. Res. Commun. 2003, 301:317-323.
62. Mueller C.M., Zhang H., Zenilman M.E. Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells. J. Surg. Res. 2008, 150:137-143.
63. Nadanaka S., Kagiyama S., Kitagawa H. Roles of EXTL2, a member of EXT family of tumor suppressors, in liver injury and regeneration processes. Biochem. J. 2013, 454:133-145.
64. Nadanaka S., Zhou S., Kagiyama S., Shoji N., Sugahara K., Sugihara K., Asano M., Kitagawa H. EXTL2, a member of the EXT family of tumor suppressors, controls glycosaminoglycan biosynthesis in a xylose kinase-dependent manner. J. Biol. Chem. 2013, 288:9321-9333.
65. Okada M., Nadanaka S., Shoji N., Tamura J., Kitagawa H. Biosynthesis of heparan sulfate in EXT1-deficient cells. Biochem. J. 2010, 428:463-471.
66. Parikh A., Stephan A.F., Tzanakakis E.S. Regenerating proteins and their expression, regulation and signaling. Biomol. Concepts 2012, 3:57-70.
67. Pedersen L.C., Dong J., Taniguchi F., Kitagawa H., Krahn J.M., Pedersen L.G., Sugahara K., Negishi M. Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis. J. Biol. Chem. 2003, 278:14420-14428.
68. Piao Z., Kim H., Jeon B.K., Lee W.J., Park C. Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma. Cancer 1997, 80:865-872.
69. Presto J., Thuveson M., Carlsson P., Busse M., Wilen M., Eriksson I., Kusche-Gullberg M., Kjellen L. Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression and heparan sulfate sulfation. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:4751-4756.
70. Roehl H.H., Pacifici M. Shop talk: sugars, bones, and a disease called multiple hereditary exostoses. Dev. Dyn. 2010, 239:1901-1904.
71. Ropero S., Setien F., Espada J., Fraga M.F., Herranz M., Asp J., Benassi M.S., Franchi A., Patino A., Ward L.S., et al. Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells. Hum. Mol. Genet. 2004, 13:2753-2765.
72. Sarrazin S., Lamanna W.C., Esko J.D. Heparan sulfate proteoglycans. Cold Spring Harb. Perspect. Biol. 2011, 3:a004952.
73. Senay C., Lind T., Muguruma K., Tone Y., Kitagawa H., Sugahara K., Lidholt K., Lindahl U., Kusche-Gullberg M. The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis. EMBO Rep. 2000, 1:282-286.
74. Siekmann A.F., Brand M. Distinct tissue-specificity of three zebrafish ext1 genes encoding proteoglycan modifying enzymes and their relationship to somitic Sonic hedgehog signaling. Dev. Dyn. 2005, 232:498-505.
75. Simmons A.D., Musy M.M., Lopes C.S., Hwang L.Y., Yang Y.P., Lovett M. A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses. Hum. Mol. Genet. 1999, 8:2155-2164.
76. Stickens D., Clines G., Burbee D., Ramos P., Thomas S., Hogue D., Hecht J.T., Lovett M., Evans G.A. The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nat. Genet. 1996, 14:25-32.
77. Stickens D., Brown D., Evans G.A. EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis. Dev. Dyn. 2000, 218:452-464.
78. Stickens D., Zak B.M., Rougier N., Esko J.D., Werb Z. Mice deficient in Ext2 lack heparan sulfate and develop exostoses. Development 2005, 132:5055-5068.
79. Takahashi I., Noguchi N., Nata K., Yamada S., Kaneiwa T., Mizumoto S., Ikeda T., Sugihara K., Asano M., Yoshikawa T., et al. Important role of heparan sulfate in postnatal islet growth and insulin secretion. Biochem. Biophys. Res. Commun. 2009, 383:113-118.
80. Takei Y., Ozawa Y., Sato M., Watanabe A., Tabata T. Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development 2004, 131:73-82.
81. Tao Q., Yokota C., Puck H., Kofron M., Birsoy B., Yan D., Asashima M., Wylie C.C., Lin X., Heasman J. Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell 2005, 120:857-871.
82. The I., Bellaiche Y., Perrimon N. Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol. Cell 1999, 4:633-639.
83. Toyoda H., Kinoshita-Toyoda A., Fox B., Selleck S.B. Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes. J. Biol. Chem. 2000, 275:21856-21861.
84. Tsuda M., Kamimura K., Nakato H., Archer M., Staatz W., Fox B., Humphrey M., Olson S., Futch T., Kaluza V., et al. The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila. Nature 1999, 100:276-280.
85. Van Hul W., Wuyts W., Hendrickx J., Speleman F., Wauters J., De Boulle K., Van Roy N., Bossuyt P., Willems P.J. Identification of a third EXT-like gene (EXTL3) belonging to the EXT gene family. Genomics 1998, 47:230-237.
86. Wei G., Bai X., Gabb M.M., Bame K.J., Koshy T.I., Spear P.G., Esko J.D. Location of the glucuronosyltransferase domain in the heparan sulfate copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants. J. Biol. Chem. 2000, 275:27733-27740.
87. Wise C.A., Clines G.A., Massa H., Trask B.J., Lovett M. Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family. Genome Res. 1997, 7:10-16.
88. Wu Y.Q., Heutink P., de Vries B.B., Sandkuijl L.A., van den Ouweland A.M., Niermeijer M.F., Galjaard H., Reyniers E., Willems P.J., Halley D.J. Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11. Hum. Mol. Genet. 1994, 3:167-171.
89. Wuyts W., Ramlakhan S., Van Hul W., Hecht J.T., van den Ouweland A.M., Raskind W.H., Hofstede F.C., Reyniers E., Wells D.E., de Vries B., et al. Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11. Am. J. Hum. Genet. 1995, 57:382-387.
90. Wuyts W., Van Hul W., Hendrickx J., Speleman F., Wauters J., De Boulle K., Van Roy N., Van Agtmael T., Bossuyt P., Willems P.J. Identification and characterization of a novel member of the EXT gene family, EXTL2. Eur. J. Hum. Genet. 1997, 5:382-389.
91. Yamada S., Busse M., Ueno M., Kelly O.G., Skarnes W.C., Sugahara K., Kusche-Gullberg M. Embryonic fibroblasts with a gene trap mutation in Ext1 produce short heparan sulfate chains. J. Biol. Chem. 2004, 279:32134-32141.
92. Yamaguchi Y., Inatani M., Matsumoto Y., Ogawa J., Irie F. Roles of heparan sulfate in mammalian brain development current views based on the findings from Ext1 conditional knockout studies. Prog. Mol. Biol. Transl. Sci. 2010, 93:133-152.
93. Yoneda A., Lendorf M.E., Couchman J.R., Multhaupt H.A. Breast and ovarian cancers: a survey and possible roles for the cell surface heparan sulfate proteoglycans. J. Histochem. Cytochem. 2012, 60:9-21.
94. Zak B.M., Crawford B.E., Esko J.D. Hereditary multiple exostoses and heparan sulfate polymerization. Biochim. Biophys. Acta 2002, 1573:346-355.
95. Zhang L., Esko D.J. Accumulation of a pentasaccharide terminating in a-N-acetylglucosamine in an animal cell mutant defective in heparan sulfate biosynthesis. J. Biol. Chem. 1995, 270:12557-12562.