論文 - 詳細
| RRC ID | 44614 |
|---|---|
| 著者 | Kim JS, Kim EJ, Oh JS, Park IC, Hwang SG. |
| タイトル | CIP2A modulates cell-cycle progression in human cancer cells by regulating the stability and activity of Plk1. |
| ジャーナル | Cancer Res |
| Abstract |
Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1-dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development. |
| 巻・号 | 73(22) |
| ページ | 6667-78 |
| 公開日 | 2013-11-15 |
| DOI | 10.1158/0008-5472.CAN-13-0888 |
| PII | 0008-5472.CAN-13-0888 |
| PMID | 23983103 |
| MeSH | Animals Autoantigens / physiology* Cell Cycle / drug effects Cell Cycle / genetics* Cell Cycle Proteins / metabolism* Enzyme Activation / drug effects Enzyme Activation / genetics Enzyme Stability / drug effects Gene Expression Regulation, Neoplastic / drug effects HEK293 Cells HeLa Cells Humans Intracellular Signaling Peptides and Proteins Membrane Proteins / antagonists & inhibitors Membrane Proteins / physiology* Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology* Protein Serine-Threonine Kinases / metabolism* Proto-Oncogene Proteins / metabolism* RNA, Small Interfering / pharmacology Sf9 Cells Spodoptera |
| IF | 9.727 |
| 引用数 | 41 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 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 | (FUCCI)-expressing HeLa |