Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells
| Autor: | Roderick Brathwaite, Yanhui Hu, Xiaochun Ni, Martha L. Bulyk, Donghui Yang-Zhou, Laura M. Sack, Jonathan Zirin, Stephen J. Elledge, Norbert Perrimon |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cell Survival Nucleolus Growth control Cellular biosynthesis Biology Corrections Cell Line Amino Acyl-tRNA Synthetases Animals Genetically Modified chemistry.chemical_compound Neoplasms medicine Animals Drosophila Proteins Humans Insulin Gene Oncogene Activation Multidisciplinary Aminoacyl tRNA synthetase Cancer Epithelial Cells Biological Sciences medicine.disease Cell biology DNA-Binding Proteins Gene Expression Regulation Neoplastic chemistry Transfer RNA Female RNA Interference Signal Transduction Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:14614-14619 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of Drosophila genes that are insulin-responsive and also regulate nucleolus size, we enriched for Myc target genes required for cellular biosynthesis. Among these, we identified the aminoacyl tRNA synthetases (aaRSs) as essential mediators of Myc growth control in Drosophila and found that their pharmacologic inhibition is sufficient to kill MYC-overexpressing human cells, indicating that aaRS inhibitors might be used to selectively target MYC-driven cancers. We suggest a general principle in which oncogenic increases in cellular biosynthesis sensitize cells to disruption of protein homeostasis. |
| Databáze: | OpenAIRE |
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