O-GlcNAcylation determines the function of the key O-GalNAc glycosyltransferase C1GalT1 in bladder cancer

• Published in: Acta biochimica et biophysica Sinica Vol. 56; no. 8; pp. 1108 - 1117
• Main Authors: Jiang, Yazhuo, Wu, Jinpeng, Guan, Feng, Liang, Liang, Wang, Yili
• Format: Journal Article
• Language: English
• Published: China China Science Publishing & Media Ltd 01.08.2024
• Subjects: Acetylgalactosamine - metabolism; Acetylglucosamine - metabolism; bladder cancer; C1GalT1; Cell Line, Tumor; Galactosyltransferases - genetics; Galactosyltransferases - metabolism; Glycosylation; Host Cell Factor C1; Humans; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; O-GlcNAc modification; Protein Processing, Post-Translational; T antigen; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; C1GalT1; T antigen; bladder cancer; O-GlcNAc modification
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.3724/abbs.2024129

Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 β-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.