論文 - 詳細
| RRC ID | 44079 |
|---|---|
| 著者 | Fukawa T, Ono M, Matsuo T, Uehara H, Miki T, Nakamura Y, Kanayama HO, Katagiri T. |
| タイトル | DDX31 regulates the p53-HDM2 pathway and rRNA gene transcription through its interaction with NPM1 in renal cell carcinomas. |
| ジャーナル | Cancer Res |
| Abstract |
Studies of renal cell carcinoma (RCC) have led to the development of new molecular-targeted drugs but its oncogenic origins remain poorly understood. Here, we report the identification and critical roles in renal carcinogenesis for DDX31, a novel nucleolar protein upregulated in the vast majority of human RCC. Immunohistochemical overexpression of DDX31 was an independent prognostic factor for patients with RCC. RNA interference (RNAi)-mediated attenuation of DDX31 in RCC cells significantly suppressed outgrowth, whereas ectopic DDX31 overexpression in human 293 kidney cells drove their proliferation. Endogenous DDX31 interacted and colocalized with nucleophosmin (NPM1) in the nucleoli of RCC cells, and attenuation of DDX31 or NPM1 expression decreased pre-ribosomal RNA biogenesis. Notably, in DDX31-attenuated cells, NPM1 was translocated from nucleoli to the nucleoplasm or cytoplasm where it bound to HDM2. As a result, HDM2 binding to p53 was reduced, causing p53 stablization with concomitant G(1) phase cell-cycle arrest and apoptosis. Taken together, our findings define a mechanism through which control of the DDX31-NPM1 complex is likely to play critical roles in renal carcinogenesis. |
| 巻・号 | 72(22) |
| ページ | 5867-77 |
| 公開日 | 2012-11-15 |
| DOI | 10.1158/0008-5472.CAN-12-1645 |
| PII | 0008-5472.CAN-12-1645 |
| PMID | 23019224 |
| MeSH | Animals COS Cells Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / metabolism Cell Nucleolus / genetics Cell Nucleolus / metabolism DEAD-box RNA Helicases / biosynthesis DEAD-box RNA Helicases / genetics* DEAD-box RNA Helicases / metabolism HEK293 Cells Humans Immunohistochemistry Kidney Neoplasms / genetics* Kidney Neoplasms / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism Nucleophosmin Prognosis Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 / metabolism* RNA, Ribosomal / genetics* Signal Transduction Transcription, Genetic Transfection Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Up-Regulation |
| IF | 9.727 |
| 引用数 | 22 |
| 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 | 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 | |