顺铂
乙酰化
膀胱癌
活力测定
泛素连接酶
癌症研究
泛素
细胞生长
蛋白质降解
癌症
化学
医学
内科学
细胞凋亡
生物
细胞生物学
基因
化疗
生物化学
作者
Miner Xie,Liwen Zhou,Li T,Yi Lin,Ruhua Zhang,X.F. Steven Zheng,Cuiling Zeng,Zheng Li,Li Zhong,Xiao-Dan Huang,Yao Zou,Tiebang Kang,Yuanzhong Wu
标识
DOI:10.1002/advs.202310146
摘要
Bladder cancer (BC) is one of the most common tumors characterized by a high rate of relapse and a lack of targeted therapy. Here, YEATS domain-containing protein 4 (YEATS4) is an essential gene for BC cell viability using CRISPR-Cas9 library screening is reported, and that HUWE1 is an E3 ligase responsible for YEATS4 ubiquitination and proteasomal degradation by the Protein Stability Regulators Screening Assay. KAT8-mediated acetylation of YEATS4 impaired its interaction with HUWE1 and consequently prevented its ubiquitination and degradation. The protein levels of YEATS4 and KAT8 are positively correlated and high levels of these two proteins are associated with poor overall survival in BC patients. Importantly, suppression of YEATS4 acetylation with the KAT8 inhibitor MG149 decreased YEATS4 acetylation, reduced cell viability, and sensitized BC cells to cisplatin treatment. The findings reveal a critical role of the KAT8/YEATS4 axis in both tumor growth and cisplatin sensitivity in BC cells, potentially generating a novel therapeutic strategy for BC patients.
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