Citation:
Zirin J, Ni X, Sack LM, Yang-Zhou D, Hu Y, Brathwaite R, et al. Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells. Proc Natl Acad Sci U S A. 2019;
 | 2019_PNAS_Zirin.pdf | 1.58 MB |
| Supplement.pdf | 498 KB |
 | Supp. Datasets.zip | 3.56 MB |
Date Published:
2019 Jul 01Abstract:
Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of 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 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.See also: Research Article
