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

作　　者：Yazhuo Jiang Jinpeng Wu Feng Guan Liang Liang Yili Wang 

机构地区：[1]Institute for Cancer Research,School of Basic Medical Science,Xi’an Jiaotong University,Xi’an 710061,China [2]Department of Urology,the Third Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710068,China [3]Key Laboratory of Resource Biology and Biotechnology in Western China,Ministry of Education,Provincial Key Laboratory of Biotechnology,College of Life Sciences,Northwest University,Xi’an 710069,China [4]Department of Urology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第8期1108-1117,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grant from the Science and Technology Development of Shaanxi Province,China(No.2023-YBSF-004).

摘　　要：Protein glycosylation is a type of protein post-translational modification.One specific example is the modification of proteins with O-linkedβ-N-acetylglucosamine(O-GlcNAc)and O-linkedα-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 core1β-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.

关 键 词：C1GalT1 O-GlcNAc modification bladder cancer T antigen 

分 类 号：R737.14[医药卫生—肿瘤]