Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells

Inhibition of CTPS in MYC-overexpressing cells blocks pyrimidine synthesis while maintaining ribosome synthesis activity to create an anabolic imbalance that induces replication stress, providing a new approach to selectively target MYC-driven cancer.

[1]  G. Lu,et al.  Structural basis for ligand binding modes of CTP synthase , 2021, Proceedings of the National Academy of Sciences.

[2]  Smita Y. Patel,et al.  Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation. , 2020, JCI insight.

[3]  H. Xiang,et al.  CTP synthase forms cytoophidia in archaea , 2019, bioRxiv.

[4]  Mihai I Truica,et al.  Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. , 2019, Cancer cell.

[5]  J. Kollman,et al.  Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments , 2019, bioRxiv.

[6]  Ji-Long Liu,et al.  Forming cytoophidia prolongs the half-life of CTP synthase , 2019, Cell Discovery.

[7]  M. Guenther,et al.  Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy , 2019, Science Translational Medicine.

[8]  Ji-Long Liu,et al.  mTOR-S6K1 pathway mediates cytoophidium assembly , 2019, Journal of genetics and genomics = Yi chuan xue bao.

[9]  H. Kunz,et al.  Characterization of filament-forming CTP synthases from Arabidopsis thaliana. , 2018, The Plant journal : for cell and molecular biology.

[10]  J. Kollman,et al.  Human CTP synthase filament structure reveals the active enzyme conformation , 2017, Nature Structural &Molecular Biology.

[11]  Ji-Long Liu.  The Cytoophidium and Its Kind: Filamentation and Compartmentation of Metabolic Enzymes. , 2016, Annual review of cell and developmental biology.

[12]  Gabriel N. Aughey,et al.  The Interplay between Myc and CTP Synthase in Drosophila , 2016, PLoS genetics.

[13]  C. Dang,et al.  MYC, Metabolism, and Cancer. , 2015, Cancer discovery.

[14]  M. McKeown,et al.  Therapeutic strategies to inhibit MYC. , 2014, Cold Spring Harbor perspectives in medicine.

[15]  A. Fischer,et al.  CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation , 2014, Nature.

[16]  D. Ruggero,et al.  Protein and Nucleotide Biosynthesis Are Coupled by a Single Rate-Limiting Enzyme, PRPS2, to Drive Cancer , 2014, Cell.

[17]  Ji-Long Liu,et al.  CTP synthase forms cytoophidia in the cytoplasm and nucleus. , 2014, Experimental cell research.

[18]  P. Hurlin.  Control of vertebrate development by MYC. , 2013, Cold Spring Harbor perspectives in medicine.

[19]  Chi V Dang,et al.  MYC on the Path to Cancer , 2012, Cell.

[20]  Takashi Tsukamoto,et al.  Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. , 2012, Cell metabolism.

[21]  Peder E. Z. Larson,et al.  13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. , 2011, Cell metabolism.

[22]  Brian K. Sato,et al.  Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster , 2010, The Journal of cell biology.

[23]  Hong Liu,et al.  Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase , 2010, Proceedings of the National Academy of Sciences.

[24]  G. Jensen,et al.  The metabolic enzyme CTP synthase forms cytoskeletal filaments , 2010, Nature Cell Biology.

[25]  Ji-Long Liu.  Intracellular compartmentation of CTP synthase in Drosophila. , 2010, Journal of genetics and genomics = Yi chuan xue bao.

[26]  D. Felsher,et al.  MYC as a regulator of ribosome biogenesis and protein synthesis , 2010, Nature Reviews Cancer.

[27]  K. Zeller,et al.  Global Regulation of Nucleotide Biosynthetic Genes by c-Myc , 2008, PloS one.

[28]  D. Zhuang,et al.  Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells , 2008, Cell cycle.

[29]  P. Graves,et al.  Regulation of Human Cytidine Triphosphate Synthetase 1 by Glycogen Synthase Kinase 3* , 2007, Journal of Biological Chemistry.

[30]  A. Tward,et al.  Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC , 2007, Nature Medicine.

[31]  Julie A. Wilkins,et al.  Myc deletion rescues Apc deficiency in the small intestine , 2007, Nature.

[32]  T. Traut,et al.  Physiological concentrations of purines and pyrimidines , 1994, Molecular and Cellular Biochemistry.

[33]  Kenneth Chu,et al.  Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC , 2002, Science.

[34]  P. Vreken,et al.  Identification of a cDNA encoding an isoform of human CTP synthetase. , 2000, Biochimica et biophysica acta.

[35]  M. Cole,et al.  The c-Myc Transactivation Domain Is a Direct Modulator of Apoptotic versus Proliferative Signals , 2000, Molecular and Cellular Biology.

[36]  A. Bradley,et al.  A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. , 1993, Genes & development.

[37]  M. Tarr,et al.  Evaluation of murine lymphocyte membrane potential, intracellular free calcium, and interleukin-2 receptor expression upon exposure to 1,1-dimethylhydrazine. , 1992, Toxicology letters.

[38]  P. H. Ellims,et al.  Cytidine triphosphate synthetase activity in lymphoproliferative disorders. , 1983, Cancer research.

[39]  H. Morris,et al.  Increased CTP synthetase activity in cancer cells , 1978, Nature.

[40]  D. Koshland,et al.  Cytidine triphosphate synthetase. Covalent intermediates and mechanisms of action. , 1971, Biochemistry.