Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 31262815.
- Also identified by DOI 10.1073/pnas.1821863116 and PMC identifier 6642371.
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Abstract
Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of <i>Drosophila</i> 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 <i>Drosophila</i> 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.
Medical subject headings
- Amino Acyl-tRNA Synthetases
- DNA-Binding Proteins
- Drosophila Proteins
- Gene Expression Regulation, Neoplastic
- Neoplasms
- Transcription Factors