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
收藏
页码：14614 / 14619
页数：6
相关论文
共 23 条
  • [1] Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells (vol 116, pg 14614, 2019)
    Zirin, Jonathan
    Ni, Xiaochun
    Sack, Laura M.
    Yang-Zhou, Donghui
    Hu, Yanhui
    Brathwaite, Roderick
    Bulyk, Martha L.
    Elledge, Stephen J.
    Perrimon, Norbert
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (34) : 17128 - 17128
  • [2] A high-content screen identifies the vulnerability of MYC-overexpressing cells to dimethylfasudil
    Zhang, Jing
    Zhang, Shenqiu
    Shi, Qiong
    Allen, Thaddeus D.
    You, Fengming
    Yang, Dun
    PLOS ONE, 2021, 16 (03):
  • [3] Radiosensitization of MYC-overexpressing prostate cancer cells by statins
    Salih, T.
    Aziz, K.
    Thiyagarajan, S.
    Armour, M.
    Shanmugam, B.
    Zeng, J.
    Adam, S. J.
    Felsher, D. W.
    DeWeese, T. L.
    Tran, P. T.
    JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (07)
  • [4] NUCLEAR COLOCALIZATION OF CELLULAR AND VIRAL MYC PROTEINS WITH HSP70 IN MYC-OVEREXPRESSING CELLS
    KOSKINEN, PJ
    SISTONEN, L
    EVAN, G
    MORIMOTO, R
    ALITALO, K
    JOURNAL OF VIROLOGY, 1991, 65 (02) : 842 - 851
  • [5] E2F activity is essential for survival of Myc-overexpressing human cancer cells
    Eric Santoni-Rugiu
    Dominique Duro
    Thomas Farkas
    Ida S Mathiasen
    Marja Jäättelä
    Jiri Bartek
    Jiri Lukas
    Oncogene, 2002, 21 : 6498 - 6509
  • [6] E2F activity is essential for survival of Myc-overexpressing human cancer cells
    Santoni-Rugiu, E
    Duro, D
    Farkas, T
    Mathiasen, IS
    Jäättelä, M
    Bartek, J
    Lukas, J
    ONCOGENE, 2002, 21 (42) : 6498 - 6509
  • [7] Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells
    Sun, Zhe
    Zhang, Ziheng
    Wang, Qiao-Qi
    Liu, Ji-Long
    CANCER RESEARCH, 2022, 82 (06) : 1013 - 1024
  • [8] Alisertib, an Aurora a Kinase Inhibitor, Induces Synthetic Lethality and Overcomes Chemoresistance in Myc-Overexpressing Lymphoma Cells
    Park, Steven I.
    Lin, Carolina P.
    Dittmer, Dirk P.
    Angus, Steven P.
    Wang, Greg G.
    Fedoriw, Yuri D.
    Darr, David B.
    Roth, Daniel P.
    Sharpless, Norman E.
    Damania, Blossom
    BLOOD, 2015, 126 (23)
  • [9] PIM1 kinase inhibition halts the growth of MYC-overexpressing triple-negative breast tumors
    Horiuchi, Dai
    Zhou, Alicia Y.
    Corella, Alexandra N.
    Yau, Christina
    Lawson, Devon A.
    Bazarov, Alexey V.
    Yaswen, Paul
    McManus, Michael T.
    Werb, Zena
    Welm, Alana L.
    Goga, Andrei
    CANCER RESEARCH, 2014, 74 (19)
  • [10] Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements
    Kumagai, T
    Tanio, Y
    Osaki, T
    Hosoe, S
    Tachibana, I
    Ueno, K
    Kijima, T
    Horai, T
    Kishimoto, T
    CANCER RESEARCH, 1996, 56 (02) : 354 - 358
123