重庆医科大学汪凯的科学博客分享 http://blog.sciencenet.cn/u/Kwang02 重医感染性疾病分子生物学教育部重点实验室——汪凯的个人主页

博文

Oncogene: E3泛素连接酶SKP2的O-GlcNAc糖基化修饰促进肝癌增殖的机制研究

已有 463 次阅读 2024-2-24 10:38 |系统分类:论文交流

O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation

Zhongqi Feng, Jiaxin Yin, Zhirong Zhang, Zhen Chen, Luyi Huang*, Ni Tang*, Kai Wang* 

  细胞S期激酶相关蛋白2(SKP2,也称为p45)是一种重要的E3泛素连接酶,在细胞周期的调控中发挥关键功能。我们发现SKP2蛋白的34位丝氨酸发生O-GlcNAc糖基化修饰,O-GlcNAc修饰与泛素化修饰两种PTM之间的交互作用在调节肝细胞癌增殖中起着重要作用;为肝癌的治疗提供了潜在的新靶点。

Abstract

O-linked-β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) and ubiquitination are critical posttranslational modifications that regulate tumor development and progression. The continuous progression of the cell cycle is the fundamental cause of tumor proliferation. S-phase kinase-associated protein 2 (SKP2), an important E3 ubiquitin ligase, assumes a pivotal function in the regulation of the cell cycle. However, it is still unclear whether SKP2 is an effector of O-GlcNAcylation that affects tumor progression. In this study, we found that SKP2 interacted with O-GlcNAc transferase (OGT) and was highly O-GlcNAcylated in hepatocellular carcinoma (HCC). Mechanistically, the O-GlcNAcylation at Ser34 stabilized SKP2 by reducing its ubiquitination and degradation mediated by APC-CDH1. Moreover, the O-GlcNAcylation of SKP2 enhanced its binding ability with SKP1, thereby enhancing its ubiquitin ligase function. Consequently, SKP2 facilitated the transition from the G1-S phase of the cell cycle by promoting the ubiquitin degradation of cell cycle-dependent kinase inhibitors p27 and p21. Additionally, targeting the O-GlcNAcylation of SKP2 significantly suppressed the proliferation of HCC. Altogether, our findings reveal that O-GlcNAcylation, a novel posttranslational modification of SKP2, plays a crucial role in promoting HCC proliferation, and targeting the O-GlcNAcylation of SKP2 may become a new therapeutic strategy to impede the progression of HCC.

SKP2糖基化.jpg

科学假说模式图

DOIhttps://doi.org/10.1038/s41388-024-02977-7

Full texthttps://www.nature.com/articles/s41388-024-02977-7 



https://blog.sciencenet.cn/blog-446272-1422852.html

上一篇:重庆彩云湖湿地公园徒步
下一篇:NCB: 胰腺癌相关的成纤维细胞-乙酸-多胺代谢促肿瘤生长的分子机制研究
收藏 IP: 125.84.75.*| 热度|

2 宁利中 杨正瓴

该博文允许注册用户评论 请点击登录 评论 (0 个评论)

数据加载中...

Archiver|手机版|科学网 ( 京ICP备07017567号-12 )

GMT+8, 2024-4-23 12:23

Powered by ScienceNet.cn

Copyright © 2007- 中国科学报社

返回顶部