論文 - 詳細
| RRC ID | 10977 |
|---|---|
| 著者 | Matsumura I, Kitamura T, Wakao H, Tanaka H, Hashimoto K, Albanese C, Downward J, Pestell RG, Kanakura Y. |
| タイトル | Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells. |
| ジャーナル | EMBO J |
| Abstract |
STAT5 is a member of a family of transcription factors that participate in the signal transduction pathways of many hormones and cytokines. Although STAT5 is suggested to play a crucial role in the biological effects of cytokines, its downstream target(s) associated with cell growth control is largely unknown. In a human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-rasG12V) enabled F-36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6-STAT5A and H-rasG12V individually and cooperatively transactivated the cyclin D1 promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced cyclin D1 promoter activities in F-36P-mpl cells. Using a series of mutant cyclin D1 promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter through the potential STAT-binding sequence at -481 bp. In electrophoretic mobility shift assays, STAT5 bound to the element in response to IL-3. Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was restored by expression of cyclin D1. Thus STAT5, in addition to ras signaling, appears to mediate transcriptional regulation of cyclin D1, thereby contributing to cytokine-dependent growth of hematopoietic cells. |
| 巻・号 | 18(5) |
| ページ | 1367-77 |
| 公開日 | 1999-3-1 |
| DOI | 10.1093/emboj/18.5.1367 |
| PMID | 10064602 |
| PMC | PMC1171226 |
| MeSH | Cell Cycle / genetics Cell Division / drug effects Cell Line Cyclin D1 / genetics* Cyclin D2 Cyclins / genetics DNA-Binding Proteins / analysis DNA-Binding Proteins / genetics* Gene Expression Regulation / genetics Genes, Reporter / genetics Hematopoietic Stem Cells* Humans Interleukin-3 / pharmacology Milk Proteins* Promoter Regions, Genetic / genetics* RNA, Messenger / metabolism STAT5 Transcription Factor Suppression, Genetic / genetics Trans-Activators / genetics* Transcription, Genetic Transcriptional Activation / genetics Transfection Tumor Suppressor Proteins ras Proteins / genetics |
| 引用数 | 126 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY VIROLOGY |
| 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 | 8 |
| 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 | F-36P(RCB0775) |