論文 - 詳細
| RRC ID | 69232 |
|---|---|
| 著者 | Taira N, Mimoto R, Kurata M, Yamaguchi T, Kitagawa M, Miki Y, Yoshida K. |
| タイトル | DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells. |
| ジャーナル | J Clin Invest |
| Abstract |
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 β (GSK3β). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this GSK3β 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. |
| 巻・号 | 122(3) |
| ページ | 859-72 |
| 公開日 | 2012-3-1 |
| DOI | 10.1172/JCI60818 |
| PII | 60818 |
| PMID | 22307329 |
| PMC | PMC3287383 |
| MeSH | Animals Cell Cycle Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Enzymologic* Gene Expression Regulation, Neoplastic* HeLa Cells Humans JNK Mitogen-Activated Protein Kinases / metabolism* Male Mice Mice, Inbred BALB C Neoplasm Transplantation Phosphorylation Protein Serine-Threonine Kinases / metabolism Protein Serine-Threonine Kinases / physiology* Protein-Tyrosine Kinases / metabolism Protein-Tyrosine Kinases / physiology* Proto-Oncogene Proteins c-myc / metabolism* |
| IF | 11.864 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) |