期刊
MOLECULAR CARCINOGENESIS
卷 60, 期 10, 页码 702-714出版社
WILEY
DOI: 10.1002/mc.23336
关键词
breast cancer (BC); monocarboxylate transporter 4 (MCT4); posttranslational modifications (PTMs); SUMOylation; ubiquitination
资金
- National Natural Science Foundation of China [31770968, 31800661]
The study revealed that SUMOylation of MCT4 stabilizes its protein levels in breast cancer, with K448 being crucial for this process. Mutations of K448 in MCT4 could potentially have therapeutic significance in breast cancer treatment.
Monocarboxylate transporter 4 (MCT4) is highly expressed in various types of solid neoplasms including breast cancer (BC); however, the pro-tumor functions underlying its increased expression have not been explained. Here, we examined the roles of posttranslational modifications to MCT4 in BC, particularly SUMOylation. Our findings revealed that SUMOylation of MCT4 inhibited its degradation and stabilized MCT4 protein levels, while ubiquitination facilitated MCT4 degradation. The E3 ubiquitin ligases beta-TRCP and FBW7 interacted with MCT4 at the DSG-box and TPETS sequences, respectively, and Lys448 (K448) of MCT4 could be modified by SUMO chains. Our key finding was that K448 was crucial for MCT4 SUMOylation. Moreover, mutations of K448 abolished MCT4 expression, delaying the growth of BC. This study suggested that SUMOylation of K448 increased MCT4 levels, and mutations of K448 in MCT4 could have therapeutic significance in BC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据