Cosmc is an essential chaperone for correct protein O-glycosylation
Open Access
- 3 May 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (20), 9228-9233
- https://doi.org/10.1073/pnas.0914004107
Abstract
Cosmc is a molecular chaperone thought to be required for expression of active T-synthase, the only enzyme that galactosylates the Tn antigen (GalNAcα1-Ser/Thr-R) to form core 1 Galβ1–3GalNAcα1-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.Keywords
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