Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase-4
文献类型：期刊论文
| 作者 | Sun, Y.1; Cao, S.2; Yang, M.1; Wu, S.1; Wang, Z.1; Lin, X.3; Song, X.4; Liao, D. J.1 |
| 刊名 | ONCOGENE
 |
| 出版日期 | 2013-04-01 |
| 卷号 | 32期号:14页码:1794-1810 |
| 关键词 | PRS6KA6 RSK4 alternative splicing breast cancer pancreatic cancer |
| ISSN号 | 0950-9232 |
| 通讯作者 | Cao, S |
| 中文摘要 | The RPS6KA6 gene encodes the p90 ribosomal S6 kinase-4 (RSK4) that is still largely uncharacterized. In this study we identified a new RSK4 transcription initiation site and several alternative splice sites with a 5'-RACE approach. The resulting mRNA variants encompass four possible first start codons. The first 15 nucleotides (nt) of exon 22 in mouse and the penultimate exon in both human (exon 21) and mouse (exon 24) RSK4 underwent alternative splicing, although the penultimate exon deleted variant appeared mainly in cell clines, but not in most normal tissues. Demethylation agent 5-azacytidine inhibited the deletion of the penultimate exon, whereas two indolocarbazole-derived inhibitors of cyclin-dependent kinase 4 or 6 induced deletion of the first 39 nt from exon 21 of human RSK4. In all human cancer cell lines studied, the 90-kDa wild-type RSK4 was sparse but, surprisingly, several isoforms at or smaller than 72 kDa were expressed as detected by seven different antibodies. On immunoblots, each of these smaller isoforms often appeared as a duplet or triplet and the levels of these isoforms varied greatly among different cell lines and culture conditions. Cyclin D1 inhibited RSK4 expression and serum starvation enhanced the inhibition, whereas c-Myc and RSK4 inhibited cyclin D1. The effects of RSK4 on cell growth, cell death and chemoresponse depended on the mRNA variant or the protein isoform expressed, on the specificity of the cell lines, as well as on the anchorage-dependent or -independent growth conditions and the in vivo situation. Moreover, we also observed that even a given cDNA might be expressed to multiple proteins; therefore, when using a cDNA, one needs to exclude this possibility before attribution of the biological results from the cDNA to the anticipated protein. Collectively, our results suggest that whether RSK4 is oncogenic or tumor suppressive depends on many factors. Oncogene (2013) 32, 1794-1810; doi: 10.1038/onc.2012.200; published online 21 May 2012 |
| 英文摘要 | The RPS6KA6 gene encodes the p90 ribosomal S6 kinase-4 (RSK4) that is still largely uncharacterized. In this study we identified a new RSK4 transcription initiation site and several alternative splice sites with a 5'-RACE approach. The resulting mRNA variants encompass four possible first start codons. The first 15 nucleotides (nt) of exon 22 in mouse and the penultimate exon in both human (exon 21) and mouse (exon 24) RSK4 underwent alternative splicing, although the penultimate exon deleted variant appeared mainly in cell clines, but not in most normal tissues. Demethylation agent 5-azacytidine inhibited the deletion of the penultimate exon, whereas two indolocarbazole-derived inhibitors of cyclin-dependent kinase 4 or 6 induced deletion of the first 39 nt from exon 21 of human RSK4. In all human cancer cell lines studied, the 90-kDa wild-type RSK4 was sparse but, surprisingly, several isoforms at or smaller than 72 kDa were expressed as detected by seven different antibodies. On immunoblots, each of these smaller isoforms often appeared as a duplet or triplet and the levels of these isoforms varied greatly among different cell lines and culture conditions. Cyclin D1 inhibited RSK4 expression and serum starvation enhanced the inhibition, whereas c-Myc and RSK4 inhibited cyclin D1. The effects of RSK4 on cell growth, cell death and chemoresponse depended on the mRNA variant or the protein isoform expressed, on the specificity of the cell lines, as well as on the anchorage-dependent or -independent growth conditions and the in vivo situation. Moreover, we also observed that even a given cDNA might be expressed to multiple proteins; therefore, when using a cDNA, one needs to exclude this possibility before attribution of the biological results from the cDNA to the anticipated protein. Collectively, our results suggest that whether RSK4 is oncogenic or tumor suppressive depends on many factors. Oncogene (2013) 32, 1794-1810; doi: 10.1038/onc.2012.200; published online 21 May 2012 |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 类目[WOS] | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 关键词[WOS] | X-LINKED GENES ; TRANSLATIONAL REGULATION ; C-MYC ; MESSENGER-RNA ; BREAST-CANCER ; CYCLIN D1 ; INDUCED SENESCENCE ; PANCREATIC-CANCER ; TRANSGENIC MOUSE ; OVARIAN-CANCER |
| 收录类别 | SCI |
| 原文出处 | 10.1038/onc.2012.200 |
| 语种 | 英语 |
| WOS记录号 | WOS:000317043900006 |
| 公开日期 | 2014-07-17 |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/16290]  |
| 专题 | 海洋研究所_海洋地质与环境重点实验室 |
| 作者单位 | 1.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA 2.Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA 3.Chinese Acad Sci, Inst Oceanol, Qingdao, Peoples R China 4.Shandong Canc Hosp & Inst, Shandong Prov Key Lab Radiat Oncol, Jinan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Y.,Cao, S.,Yang, M.,et al. Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase-4[J]. ONCOGENE,2013,32(14):1794-1810. |
| APA | Sun, Y..,Cao, S..,Yang, M..,Wu, S..,Wang, Z..,...&Liao, D. J..(2013).Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase-4.ONCOGENE,32(14),1794-1810. |
| MLA | Sun, Y.,et al."Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase-4".ONCOGENE 32.14(2013):1794-1810. |
入库方式： OAI收割
来源：海洋研究所
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