Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/nature22315 |
Translation from unconventional 5 ' start sites drives tumour initiation | |
Sendoel, Ataman1; Dunn, Joshua G.2; Rodriguez, Edwin H.2; Naik, Shruti1; Gomez, Nicholas C.1; Hurwitz, Brian1; Levorse, John1; Dill, Brian D.3; Schramek, Daniel1,4; Molina, Henrik3; Weissman, Jonathan S.2; Fuchs, Elaine1 | |
2017-01-26 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 541期号:7638页码:494-499 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Canada |
英文摘要 | We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific, in vivo ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy. Using a mouse model of inducible SOX2, which is broadly expressed in oncogenic RAS-associated cancers, we show that despite widespread reductions in translation and protein synthesis, certain oncogenic mRNAs are spared. During tumour initiation, the translational apparatus is redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs. An in vivo RNA interference screen of translational regulators revealed that depletion of conventional eIF2 complexes has adverse effects on normal but not oncogenic growth. Conversely, the alternative initiation factor eIF2A is essential for cancer progression, during which it mediates initiation at these upstream sites, differentially skewing translation and protein expression. Our findings unveil a role for the translation of 5' untranslated regions in cancer, and expose new targets for therapeutic intervention. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000396116600043 |
WOS关键词 | OPEN READING FRAMES ; STEM-CELL ; MALIGNANT-TRANSFORMATION ; PROTEIN-SYNTHESIS ; GENE-EXPRESSION ; IN-VIVO ; SOX2 ; IDENTIFICATION ; POPULATIONS ; REGULATORS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202738 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Rockefeller Univ, Robin Chemers Neustein Lab Mammalian Dev & Cell B, Howard Hughes Med Inst, New York, NY 10065 USA; 2.Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Howard Hughes Med Inst, San Francisco, CA 94158 USA; 3.Rockefeller Univ, Prote Resource Ctr, New York, NY 10065 USA; 4.Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada |
推荐引用方式 GB/T 7714 | Sendoel, Ataman,Dunn, Joshua G.,Rodriguez, Edwin H.,et al. Translation from unconventional 5 ' start sites drives tumour initiation[J]. NATURE,2017,541(7638):494-499. |
APA | Sendoel, Ataman.,Dunn, Joshua G..,Rodriguez, Edwin H..,Naik, Shruti.,Gomez, Nicholas C..,...&Fuchs, Elaine.(2017).Translation from unconventional 5 ' start sites drives tumour initiation.NATURE,541(7638),494-499. |
MLA | Sendoel, Ataman,et al."Translation from unconventional 5 ' start sites drives tumour initiation".NATURE 541.7638(2017):494-499. |
条目包含的文件 | 条目无相关文件。 |
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