细胞周期检查点
生物
细胞周期
癌症研究
细胞生物学
下调和上调
细胞生长
泛素
信号转导
癌基因
G1期
细胞
生物化学
基因
作者
Seul Gi Lee,Seon Min Woo,Seung Un Seo,Hyun‐Shik Lee,Sang Hyun Kim,Young‐Chae Chang,Hyo Je Cho,Simmyung Yook,Ju-Ock Nam,Taeg Kyu Kwon
出处
期刊:Oncogene
[Springer Nature]
日期:2024-04-25
标识
DOI:10.1038/s41388-024-03042-z
摘要
Abstract The deubiquitinase OTUB1, implicated as a potential oncogene in various tumors, lacks clarity in its regulatory mechanism in tumor progression. Our study investigated the effects and underlying mechanisms of OTUB1 on the breast cancer cell cycle and proliferation in IFNγ stimulation. Loss of OTUB1 abrogated IFNγ-induced cell cycle arrest by regulating p27 protein expression, whereas OTUB1 overexpression significantly enhanced p27 expression even without IFNγ treatment. Tyr26 phosphorylation residue of OTUB1 directly bound to p27, modulating its post-translational expression. Furthermore, we identified crucial lysine residues (K134, K153, and K163) for p27 ubiquitination. Src downregulation reduced OTUB1 and p27 expression, suggesting that IFNγ-induced cell cycle arrest is mediated by the Src-OTUB1-p27 signaling pathway. Our findings highlight the pivotal role of OTUB1 in IFNγ-induced p27 expression and cell cycle arrest, offering therapeutic implications.
科研通智能强力驱动
Strongly Powered by AbleSci AI