論文 - 詳細
| RRC ID | 5436 |
|---|---|
| 著者 | Kawauchi K, Araki K, Tobiume K, Tanaka N. |
| タイトル | p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. |
| ジャーナル | Nat Cell Biol |
| Abstract |
Cancer cells use aerobic glycolysis preferentially for energy provision and this metabolic change is important for tumour growth. Here, we have found a link between the tumour suppressor p53, the transcription factor NF-kappaB and glycolysis. In p53-deficient primary cultured cells, kinase activities of IKKalpha and IKKbeta and subsequent NF-kappaB activity were enhanced. Activation of NF-kappaB, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3. Oncogenic Ras-induced cell transformation and acceleration of aerobic glycolysis in p53-deficient cells were suppressed in the absence of p65/NF-kappaB expression, and were restored by GLUT3 expression. It was also shown that a glycolytic inhibitor diminished the enhanced IKK activity in p53-deficient cells. Moreover, in Ras-expressing p53-deficient cells, IKK activity was suppressed by p65 deficiency and restored by GLUT3 expression. Taken together, these data indicate that p53 restricts activation of the IKK-NF-kappaB pathway through suppression of glycolysis. These results suggest that a positive-feedback loop exists, whereby glycolysis drives IKK-NF-kappaB activation, and that hyperactivation of this loop by loss of p53 is important in oncogene-induced cell transformation. |
| 巻・号 | 10(5) |
| ページ | 611-8 |
| 公開日 | 2008-5-1 |
| DOI | 10.1038/ncb1724 |
| PII | ncb1724 |
| PMID | 18391940 |
| MeSH | Animals Cell Transformation, Neoplastic* Cells, Cultured Fibroblasts / cytology Fibroblasts / physiology Genes, ras Glucose / metabolism* Glucose Transporter Type 3 / genetics Glucose Transporter Type 3 / metabolism Glycolysis / physiology I-kappa B Kinase / genetics I-kappa B Kinase / metabolism* Lactic Acid / metabolism Mice Mice, Knockout RNA Interference Signal Transduction / physiology Transcription Factor RelA / genetics Transcription Factor RelA / metabolism* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* ras Proteins / genetics ras Proteins / metabolism |
| IF | 20.042 |
| 引用数 | 371 |
| WOS 分野 | CELL BIOLOGY |
| 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 | 2 |
| 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 | |
| 実験動物マウス | RBRC00300 |