Title :
Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis
Abstract :
- Secretion of fibroblast growth factor 23 requires O-glycosylation
- Mutations in the gene encoding the glycosyltransferase polypeptide GalNAc-T3, which is involved in initiation of O-glycosylation, were recently identified as a cause of the rare autosomal recessive metabolic disorder familial tumoral calcinosis (OMIM 211900)
- Familial tumoral calcinosis is associated with hyperphosphatemia and massive ectopic calcifications
- Here, we demonstrate that the secretion of the phosphaturic factor fibroblast growth factor 23 ( FGF23 ) requires O-glycosylation, and that GalNAc-T3 selectively directs O-glycosylation in a subtilisin-like proprotein convertase recognition sequence motif , which blocks processing of FGF23
- The study suggests a novel posttranslational regulatory model of FGF23 involving competing O-glycosylation and protease processing to produce intact FGF23