Institute for Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Urology, the Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Aug 8;56(8):1108-1117. 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.
蛋白质糖基化是一种蛋白质翻译后修饰。一个具体的例子是用 O-连接的 β-N-乙酰葡萄糖胺 (O-GlcNAc) 和 O-连接的 α-N-乙酰半乳糖胺 (O-GalNAc) 修饰蛋白质。先前有报道称膀胱癌 (BlCa) 中 O-GalNAc 和 O-GlcNAc 的水平都增强了。然而，O-GalNAc 和 O-GlcNAc 之间的相互作用尚未被探索。在这里，我们发现负责延伸和成熟粘蛋白型 O-聚糖的核心 1 β-1,3-半乳糖基转移酶 (C1GalT1) 的表达水平在 BlCa 中增加。这种增加伴随着 C1GalT1 的 O-GlcNAc 修饰。这种修饰稳定了 C1GalT1 的表达，并增强了它与伴侣 Cosmc 的相互作用。在 Thr229 或 Thr233 处发生突变会减弱 C1GalT1 的稳定性，并通过蛋白酶体途径促进其降解。此外，C1GalT1 的减少通过抑制糖酵解抑制了对膀胱癌细胞的促肿瘤作用。
