期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 122, 期 3, 页码 859-872出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI60818
关键词
-
资金
- Ministry of Education, Science and Culture of Japan
- Yasuda Memorial Foundation
- Uehara Memorial Foundation
- Takeda Science Foundation
- Sankyo Foundation of Life Science
- Sato Memorial Foundation for Cancer Research
- Ichiro Kanehara Foundation
- Terumo Life Science Foundation
- Foundation for Promotion of Cancer Research
- Kobayashi Foundation for Cancer Research
- Grants-in-Aid for Scientific Research [23300347, 23650612] Funding Source: KAKEN
Dysregulation of the G(1)/S transition in the cell cycle contributes to tumor development. The oncogenic transcription factors c-Jun and c-Myc are indispensable regulators at this transition, and their aberrant expression is associated with many malignancies. Degradation of c-Jun/c-Myc is a critical process for the G(1)/S transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 beta (GSK3 beta). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this GSK3 beta modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase DYRK2 functions as a priming kinase of c-Jun and c-Myc. Knockdown of DYRK2 in human cancer cells shortened the G(1) phase and accelerated cell proliferation due to escape of c-Jun and c-Myc from ubiquitination-mediated degradation. In concert with these results, silencing DYRK2 increased cell proliferation in human cancer cells, and this promotion was completely impeded by codeprivation of c-Jun or c-Myc in vivo. We also found marked attenuation of DYRK2 expression in multiple human tumor samples. Downregulation of DYRK2 correlated with high levels of unphosphorylated c-Jun and c-Myc and, importantly, with invasiveness of human breast cancers. These results reveal that DYRK2 regulates tumor progression through modulation of c-Jun and c-Myc.
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