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Proc Natl Acad Sci U S A. 2019 Jul 16;116(29):14614-14619. doi: 10.1073/pnas.1821863116. Epub 2019 Jul 1.

Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.

Author information

1
Department of Genetics, Harvard Medical School, Boston, MA 02115.
2
Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115.
3
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
4
Department of Genetics, Harvard Medical School, Boston, MA 02115; perrimon@genetics.med.harvard.edu.

Abstract

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.

KEYWORDS:

Drosophila; MYC; cancer; nucleolus; tRNA synthetase

PMID:
31262815
PMCID:
PMC6642371
[Available on 2020-01-01]
DOI:
10.1073/pnas.1821863116

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