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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acyl-tRNA Synthetases / antagonists & inhibitors
-
Amino Acyl-tRNA Synthetases / metabolism*
-
Animals
-
Animals, Genetically Modified
-
Cell Line
-
Cell Survival / drug effects
-
Cell Survival / genetics
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Epithelial Cells
-
Female
-
Gene Expression Regulation, Neoplastic / drug effects*
-
Humans
-
Insulin / metabolism
-
Male
-
Neoplasms / drug therapy*
-
Neoplasms / genetics
-
Neoplasms / pathology
-
RNA Interference
-
Signal Transduction / drug effects
-
Signal Transduction / genetics
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
Substances
-
DNA-Binding Proteins
-
Drosophila Proteins
-
Insulin
-
Myc protein, Drosophila
-
Transcription Factors
-
Amino Acyl-tRNA Synthetases