論文 - 詳細
| RRC ID | 21827 |
|---|---|
| 著者 | Dui W, Wei B, He F, Lu W, Li C, Liang X, Ma J, Jiao R. |
| タイトル | The Drosophila F-box protein dSkp2 regulates cell proliferation by targeting Dacapo for degradation. |
| ジャーナル | Mol Biol Cell |
| Abstract |
Cell cycle progression is controlled by a complex regulatory network consisting of interacting positive and negative factors. In humans, the positive regulator Skp2, an F-box protein, has been a subject of intense investigation in part because of its oncogenic activity. By contrast, the molecular and developmental functions of its Drosophila homologue, dSkp2, are poorly understood. Here we investigate the role of dSkp2 by focusing on its functional relationship with Dacapo (Dap), the Drosophila homologue of the cyclin-dependent kinase inhibitors p21(cip1)/p27(kip1)/p57(kip2). We show that dSkp2 interacts physically with Dap and has a role in targeting Dap for ubiquitination and proteasome-mediated degradation. We present evidence that dSkp2 regulates cell cycle progression by antagonizing Dap in vivo. dSkp2 knockdown reduces cell density in the wing by prolonging the cell doubling time. In addition, the wing phenotype caused by dSkp2 knockdown resembles that caused by dap overexpression and can be partially suppressed by reducing the gene dose of dap. Our study thus documents a conserved functional relationship between dSkp2 and Dap in their control of cell cycle progression, suggesting the possibility of using Drosophila as a model system to study Skp2-mediated tumorigenesis. |
| 巻・号 | 24(11) |
| ページ | 1676-87, S1-7 |
| 公開日 | 2013-6-1 |
| DOI | 10.1091/mbc.E12-10-0772 |
| PII | mbc.E12-10-0772 |
| PMID | 23552694 |
| PMC | PMC3667721 |
| MeSH | Animals Animals, Genetically Modified Cell Cycle Cell Line Cell Proliferation Cyclin-Dependent Kinase Inhibitor p21 / genetics Cyclin-Dependent Kinase Inhibitor p21 / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Eye / metabolism Eye / pathology Gene Expression Regulation, Developmental Humans Macrophages / cytology Macrophages / metabolism* Nuclear Proteins / genetics* Nuclear Proteins / metabolism Proteasome Endopeptidase Complex / metabolism Proteolysis RNA, Small Interfering / genetics RNA, Small Interfering / metabolism S-Phase Kinase-Associated Proteins / antagonists & inhibitors S-Phase Kinase-Associated Proteins / genetics* S-Phase Kinase-Associated Proteins / metabolism Sequence Homology, Amino Acid Signal Transduction Ubiquitination Wings, Animal / metabolism Wings, Animal / pathology |
| IF | 3.791 |
| 引用数 | 10 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | 3938R-2 3938R-3 |