دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.
المؤلفون: Zirin J; Department of Genetics, Harvard Medical School, Boston, MA 02115., Ni X; Department of Genetics, Harvard Medical School, Boston, MA 02115., Sack LM; Department of Genetics, Harvard Medical School, Boston, MA 02115., Yang-Zhou D; Department of Genetics, Harvard Medical School, Boston, MA 02115., Hu Y; Department of Genetics, Harvard Medical School, Boston, MA 02115., Brathwaite R; Department of Genetics, Harvard Medical School, Boston, MA 02115., Bulyk ML; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115., Elledge SJ; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115.; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115., Perrimon N; Department of Genetics, Harvard Medical School, Boston, MA 02115; perrimon@genetics.med.harvard.edu.; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jul 16; Vol. 116 (29), pp. 14614-14619. Date of Electronic Publication: 2019 Jul 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Amino Acyl-tRNA Synthetases/*metabolism , DNA-Binding Proteins/*metabolism , Drosophila Proteins/*metabolism , Gene Expression Regulation, Neoplastic/*drug effects , Neoplasms/*drug therapy , Transcription Factors/*metabolism, Amino Acyl-tRNA Synthetases/antagonists & inhibitors ; Animals ; Animals, Genetically Modified ; Cell Line ; Cell Survival/drug effects ; Cell Survival/genetics ; DNA-Binding Proteins/genetics ; Drosophila Proteins/genetics ; Epithelial Cells ; Female ; Humans ; Insulin/metabolism ; Male ; Neoplasms/genetics ; Neoplasms/pathology ; RNA Interference ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transcription Factors/genetics
مستخلص: 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.
Competing Interests: The authors declare no conflict of interest.
التعليقات: Erratum in: Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17128. (PMID: 31405975)
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معلومات مُعتمدة: P01 CA120964 United States CA NCI NIH HHS; R01 AR057352 United States AR NIAMS NIH HHS; R01 GM084947 United States GM NIGMS NIH HHS; United States HHMI Howard Hughes Medical Institute
فهرسة مساهمة: Keywords: Drosophila; MYC; cancer; nucleolus; tRNA synthetase
المشرفين على المادة: 0 (DNA-Binding Proteins)
0 (Drosophila Proteins)
0 (Insulin)
0 (Myc protein, Drosophila)
0 (Transcription Factors)
EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
تواريخ الأحداث: Date Created: 20190703 Date Completed: 20200402 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC6642371
DOI: 10.1073/pnas.1821863116
PMID: 31262815
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1821863116