| RRC ID |
57307
|
| 著者 |
Zirin J, Ni X, Sack LM, Yang-Zhou D, Hu Y, Brathwaite R, Bulyk ML, Elledge SJ, Perrimon N.
|
| タイトル |
Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| 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.
|
| 巻・号 |
116(29)
|
| ページ |
14614-14619
|
| 公開日 |
2019-7-16
|
| DOI |
10.1073/pnas.1821863116
|
| PII |
1821863116
|
| PMID |
31262815
|
| PMC |
PMC6642371
|
| MeSH |
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*
|
| IF |
9.58
|
| 引用数 |
6
|
| リソース情報 |
| ショウジョウバエ |
11188R-2, 30170R-2, 17054R-2, 11804R-1, 10286R-1, 11523R-4,
13890R-1, 14230R-1, 1463R-2, 14641R-1, 15547R-3, 1607R-3, 17018R-1, 2225R-1, 2889R-2,
6572R-3, 32104R-1, 4611R-1, 4646R-4, 6071R-2, 6767R-1, 6928R-1, 7339R-1, 7739R-3 ,
8858R-4, 1044R-2, 8357R-2, 11166R-3, 31731R-3, 18374R-1, 5688R-1, 17530R-2, 4647R-1,
7436R-1, 1553R-1, 13849R-3 , 3424R-2, 17725R-2, 2488R-1, 7487R-3, 9606R-1, 4510R-2,
9791R-2 , 10496R-1, 4561R-2, HMJ21228, HMJ21046, HMJ21018 |
