| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007) |
