論文 - 詳細
| RRC ID | 6181 |
|---|---|
| 著者 | Shin SY, Bahk YY, Ko J, Chung IY, Lee YS, Downward J, Eibel H, Sharma PM, Olefsky JM, Kim YH, Lee B, Lee YH. |
| タイトル | Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras. |
| ジャーナル | EMBO J |
| Abstract |
The transcription factor Egr-1 functions as a key regulator in cellular growth, differentiation, and apoptosis. The loss of Egr-1 expression is closely associated with tumor development, although the molecular mechanism behind the suppression of Egr-1 is largely unknown. In this report, we show that growth factor-induced transcriptional activation of Egr-1 gene is downregulated by chronic expression of oncogenic H-Ras in NIH3T3 fibroblasts. Our results demonstrate that phosphoinositide 3-kinase (PI3K) signaling is necessary for oncogenic H-Ras-mediated reduction of Egr-1 gene expression. Aberrant activation of PI3K signaling by oncogenic Ras decreased the level of serum response factor (SRF) protein through the acceleration of proteolysis, which resulted in decreased SRF binding to the serum response element (SRE) sites within the Egr-1 promoter, leading to the suppression of Egr-1 transcription. Inhibition of PI3K signaling restored the downregulation of SRF and Egr-1 expression caused by oncogenic Ras. Our findings suggest a novel signaling mechanism by which prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines. |
| 巻・号 | 25(5) |
| ページ | 1093-103 |
| 公開日 | 2006-3-8 |
| DOI | 10.1038/sj.emboj.7600987 |
| PII | 7600987 |
| PMID | 16456537 |
| PMC | PMC1409727 |
| MeSH | 3T3 Cells Animals Cells, Cultured Class I Phosphatidylinositol 3-Kinases Down-Regulation Early Growth Response Protein 1 / antagonists & inhibitors Early Growth Response Protein 1 / genetics* Early Growth Response Protein 1 / metabolism Fibroblasts / cytology Fibroblasts / metabolism Gene Expression Regulation* Genes, ras / physiology* Mice Mitogen-Activated Protein Kinases / metabolism Phosphatidylinositol 3-Kinases / metabolism Platelet-Derived Growth Factor / pharmacology Promoter Regions, Genetic / genetics Serum Response Element / genetics Serum Response Factor / genetics Serum Response Factor / metabolism* Signal Transduction Transcription, Genetic* Transcriptional Activation |
| IF | 9.889 |
| 引用数 | 40 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY 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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| 各媒体での言及数の合計 | 0 |
| 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 | |
| 遺伝子材料 | AxCAhPTEN1 (RDB02012) |