論文 - 詳細
| RRC ID | 34862 |
|---|---|
| 著者 | Mitchell NC, Tchoubrieva EB, Chahal A, Woods S, Lee A, Lin JI, Parsons L, Jastrzebski K, Poortinga G, Hannan KM, Pearson RB, Hannan RD, Quinn LM. |
| タイトル | S6 Kinase is essential for MYC-dependent rDNA transcription in Drosophila. |
| ジャーナル | Cell Signal |
| Abstract |
Increased rates of ribosome biogenesis and biomass accumulation are fundamental properties of rapidly growing and dividing malignant cells. The MYC oncoprotein drives growth predominantly via its ability to upregulate the ribosome biogenesis program, in particular stimulating the activity of the RNA Polymerase I (Pol I) machinery to increase ribosomal RNA (rRNA) transcription. Although MYC function is known to be highly dependent on the cellular signalling context, the pathways interacting with MYC to regulate transcription of ribosomal genes (rDNA) in vivo in response to growth factor status, nutrient availability and cellular stress are only beginning to be understood. To determine factors critical to MYC-dependent stimulation of rDNA transcription in vivo, we performed a transient expression screen for known oncogenic signalling pathways in Drosophila. Strikingly, from the broad range of pathways tested, we found that ribosomal protein S6 Kinase (S6K) activity, downstream of the TOR pathway, was the only factor rate-limiting for the rapid induction of rDNA transcription due to transiently increased MYC. Further, we demonstrated that one of the mechanism(s) by which MYC and S6K cooperate is through coordinate activation of the essential Pol I transcription initiation factor TIF-1A (RRN 3). As Pol I targeted therapy is now in phase 1 clinical trials in patients with haematological malignancies, including those driven by MYC, these data suggest that therapies dually targeting Pol I transcription and S6K activity may be effective in treating MYC-driven tumours. |
| 巻・号 | 27(10) |
| ページ | 2045-53 |
| 公開日 | 2015-10-1 |
| DOI | 10.1016/j.cellsig.2015.07.018 |
| PII | S0898-6568(15)00215-6 |
| PMID | 26215099 |
| MeSH | Animals Cell Nucleolus / enzymology Cell Nucleolus / ultrastructure Compound Eye, Arthropod / enzymology Compound Eye, Arthropod / ultrastructure DNA, Ribosomal / genetics* DNA, Ribosomal / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / metabolism Nuclear Proteins / metabolism Proto-Oncogene Proteins c-myc / physiology* Ribosomal Protein S6 Kinases / physiology* Salivary Glands / enzymology Salivary Glands / ultrastructure Transcription Factors / metabolism Transcription, Genetic* |
| IF | 3.968 |
| 引用数 | 12 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | |
| ショウジョウバエ | 10539R-2 |