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

被引：13

作者：

Zirin, Jonathan ^{[1
]}

Ni, Xiaochun ^{[1
]}

Sack, Laura M. ^{[1
]}

Donghui Yang-Zhou ^{[1
]}

Hu, Yanhui ^{[1
]}

Brathwaite, Roderick ^{[1
]}

Bulyk, Martha L. ^{[1
,2
]}

Elledge, Stephen J. ^{[1
,2
,3
]}

Perrimon, Norbert ^{[1
,3
]}

机构：

[1] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA

[3] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2019年 / 116卷 / 29期

基金：

美国国家卫生研究院;

关键词：

MYC; tRNA synthetase; cancer; nucleolus; Drosophila; C-MYC; RIBOSOMAL-RNA; PROTEIN; MUTATIONS; REVEALS; INSULIN; GENES; DMYC;

D O I：

10.1073/pnas.1821863116

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：14614 / 14619

页数：6