The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Translation from unconventional 5′ start sites drives tumour initiation
Open accessAbstract
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.
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Translation control of the immune checkpoint in cancer and its therapeutic targeting
Xu, Y., Poggio, M., Jin, H. Y., Shi, Z., Forester, C. M., Wang, Y., Stumpf, C. R., Xue, L., Devericks, E., So, L., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0321-2 · Cited by 261
Metadata
- Authors
- Sendoel, A., Dunn, J. G., Rodriguez, E. H., Naik, S., Gomez, N. C., Hurwitz, B., Levorse, J., Dill, B. D., Schramek, D., Molina, H., Weissman, J. S., & Fuchs, E.
- Venue
- Nature
- Published
- 2017-01
- Volume
- 541
- Issue
- 7638
- Pages
- 494-499
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2579217144
- Cited by
- 331
- References
- 57
- FWCI
- 14.07
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- www.springer.com/tdm (tdm)
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- Sendoel, A., Dunn, J. G., Rodriguez, E. H., Naik, S., Gomez, N. C., Hurwitz, B., Levorse, J., Dill, B. D., Schramek, D., Molina, H., Weissman, J. S., & Fuchs, E. (2017). Translation from unconventional 5′ start sites drives tumour initiation. Nature. https://doi.org/10.1038/nature21036
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