title: Cosmc is an essential chaperone for correct protein O-glycosylation.
abstract: Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn antigen (GalNAcalpha1-Ser/Thr-R) to form core 1 Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen) during mucin type O-glycan biosynthesis. Here we show that ablation of the X-linked Cosmc gene in mice causes embryonic lethality and Tn antigen expression. Loss of Cosmc is associated with loss of T-synthase but not other enzymes required for glycoprotein biosynthesis, demonstrating that Cosmc is specific in vivo for the T-synthase. We generated genetically mosaic mice with a targeted Cosmc deletion and survivors exhibited abnormalities correlated with Tn antigen expression that are related to several human diseases.
authors.affiliation: Departments of Biochemistry and Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Tongzhong
authors.initials: T
authors.lastname: Ju
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Ding
authors.forename: Baoyun
authors.initials: B
authors.lastname: Xia
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D015139:Blotting, Southern; D003433:Crosses, Genetic; D053595:Embryonic Stem Cells / Q000378:metabolism; D005700:Galactosyltransferases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D020868:Gene Silencing; D006031:Glycosylation; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011134:Polysaccharides / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C514310:Cosmc protein, mouse; D018832:Molecular Chaperones; D011134:Polysaccharides; C040286:Tn antigen; D005700:Galactosyltransferases