Affinage

CTPS1

CTP synthase 1 · UniProt P17812

Round 2 corrected
Length
591 aa
Mass
66.7 kDa
Annotated
2026-04-28
63 papers in source corpus 21 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTPS1 is the dominant CTP synthase isoform that sustains de novo CTP biosynthesis in proliferating cells, with a particularly critical and non-redundant role in activated lymphocytes. Resting lymphocytes rely on salvage pathways, but antigen receptor–mediated activation triggers rapid CTPS1 upregulation—driven in part by YBX1-dependent transcription—to fuel the disproportionate CTP pool expansion required for clonal expansion; homozygous loss-of-function mutations cause severe combined immunodeficiency due to impaired T- and B-cell proliferation (PMID:24870241, PMID:8530356, PMID:34991621). Structurally, CTPS1 possesses higher intrinsic catalytic activity and weaker CTP product-feedback inhibition than CTPS2, which physically interacts with CTPS1 to dampen its activity; CTPS1 assembles into cytoophidium filaments built from tetrameric subunits whose formation requires H355 and the HSPD1 chaperone, though cytoophidia per se are dispensable for cell proliferation (PMID:34583994, PMID:37348953, PMID:40957650, PMID:39971178). CTPS1 protein stability is regulated by competing post-translational modifications—RASD2-mediated SUMOylation and INHBA-mediated protection from SMURF1-dependent ubiquitination—and its inhibition induces replication stress and S-phase arrest that synergizes lethally with ATR/CHK1 blockade in MYC-driven and other hematologic malignancies (PMID:39672102, PMID:41239468, PMID:35022212, PMID:37898670).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Establishing that de novo CTP synthesis is rate-limiting for pyrimidine pool expansion in activated T lymphocytes answered why proliferating lymphocytes cannot rely on salvage alone, framing CTPS as a metabolic gatekeeper of immune cell division.

    Evidence HPLC nucleotide quantification in PHA-stimulated primary human T cells with azaserine (CTPS inhibitor) and radiolabeled precursors

    PMID:8530356

    Open questions at the time
    • Isoform-specific contributions (CTPS1 vs CTPS2) not distinguished
    • Mechanism of CTPS upregulation upon activation unknown
  2. 2011 High

    Identification of CTPS1 as a core component of cytoophidium/rod-and-ring structures revealed that CTP synthase can polymerize into a novel cytoplasmic compartment distinct from canonical organelles, raising questions about the functional significance of enzyme filamentation.

    Evidence Immunofluorescence co-localization and GFP-CTPS1 overexpression in HeLa cells with pharmacological induction by DON and acivicin

    PMID:22220215

    Open questions at the time
    • Structural basis of filament assembly unknown
    • Whether cytoophidia regulate enzymatic activity undetermined
    • In vivo relevance of cytoophidia not addressed
  3. 2014 High

    The discovery that homozygous CTPS1 loss-of-function mutations cause human immunodeficiency established CTPS1 as the non-redundant isoform for lymphocyte proliferation and directly linked de novo CTP synthesis to adaptive immunity.

    Evidence Patient genetic analysis, lymphocyte proliferation assays, CTP pool rescue, wild-type CTPS1 complementation across multiple affected individuals

    PMID:24870241

    Open questions at the time
    • Tissue-specific requirements beyond lymphocytes not characterized
    • Why CTPS2 cannot compensate in this context unclear
  4. 2020 High

    Demonstrating that the patient CTPS1 frameshift mutant protein is catalytically normal but unstable clarified that the immunodeficiency arises from insufficient enzyme quantity rather than impaired catalysis, explaining the dose-dependent nature of the phenotype.

    Evidence Enzymatic activity assays and protein expression quantification of CTPS1 T566Dfs26X in KO leukemia cells with dose-titrated complementation

    PMID:32161190

    Open questions at the time
    • Degradation pathway responsible for mutant instability not identified
    • Whether residual CTPS1 levels vary among patients and affect clinical severity unknown
  5. 2021 High

    Cryo-EM structures of CTPS1 and CTPS2 revealed two CTP-binding inhibitory sites and the structural basis for CTPS1's weaker product inhibition, explaining its suitability for sustaining high CTP output during proliferation and enabling design of isoform-selective inhibitors.

    Evidence Cryo-EM at near-atomic resolution, enzyme kinetics with CTP titration, mutagenesis of isoform-distinguishing residue, selective inhibitor validation in primary T-cell proliferation assays

    PMID:34583994

    Open questions at the time
    • Full-length filament structure not resolved at atomic level
    • In vivo pharmacokinetics and selectivity of inhibitors untested
  6. 2021 Medium

    Detection of cytoophidia in thymocytes at the DN3-to-DP transition under physiological conditions linked CTPS filament formation to the metabolic switch accompanying pre-TCR signaling and rapid proliferation in vivo.

    Evidence Immunofluorescence of mouse thymus sections, correlation with c-Myc/pAkt/PFK, disruption by glycolysis inhibitor 2-DG

    PMID:34022203

    Open questions at the time
    • Causal role of cytoophidia versus correlation with metabolic state not distinguished
    • Isoform composition of thymocyte cytoophidia unresolved
  7. 2022 High

    Showing that CTPS1 inhibition selectively induces replication stress in MYC-overexpressing cells—and synergizes with ATR inhibition—established a mechanistic rationale for targeting CTPS1 in MYC-driven cancers, linking CTP depletion to DNA damage checkpoint dependency.

    Evidence siRNA isoform-specific knockdown, γH2AX DNA damage readouts, ATR inhibitor combinations in vitro and in xenograft models

    PMID:35022212

    Open questions at the time
    • Whether MYC directly regulates CTPS1 expression or only creates CTP demand not resolved
    • Patient-derived models not tested
  8. 2022 Medium

    Identification of YBX1 as a direct transcriptional activator of CTPS1 via promoter binding provided the first defined transcription factor driving CTPS1 upregulation in proliferating cancer cells.

    Evidence ChIP and luciferase reporter assays for YBX1–CTPS1 promoter binding; siRNA rescue experiments in triple-negative breast cancer cells

    PMID:34991621

    Open questions at the time
    • Whether YBX1 mediates TCR-stimulated CTPS1 induction in lymphocytes not tested
    • Other transcription factors likely contribute but are unidentified
  9. 2023 High

    Biochemical comparison confirmed CTPS1 has intrinsically higher catalytic activity and lower drug sensitivity than CTPS2, and large-scale dependency data validated CTPS1 as the dominant proliferative isoform across >1,000 cancer cell lines, with CTPS2 serving a backup role.

    Evidence Gene editing KO/complementation, purified enzyme kinetics with 3-deaza-uridine, public dependency database analysis

    PMID:37348953

    Open questions at the time
    • Structural basis for CTPS1's higher Vmax compared to CTPS2 not determined
    • Context-specific tissues where CTPS2 dominates remain poorly mapped
  10. 2024 Medium

    Discovery that RASD2 stabilizes CTPS1 via SUMOylation while protecting it from ubiquitination, and that INHBA shields CTPS1 from SMURF1-mediated ubiquitination, revealed two independent post-translational mechanisms controlling CTPS1 protein turnover.

    Evidence IP-MS, Co-IP, SUMOylation/ubiquitination assays, SMURF1 competition experiments; validated in endometriosis and pancreatic cancer models

    PMID:39672102 PMID:41239468

    Open questions at the time
    • SUMOylation site(s) on CTPS1 not mapped
    • Whether these mechanisms operate in lymphocytes unknown
    • Relative contribution of SMURF1 versus other E3 ligases not determined
  11. 2025 High

    Demonstration that CTPS2 directly interacts with CTPS1 to dampen its activity and increase CTP sensitivity—independently of filament formation—and that H355A cytoophidium-null mutants support normal proliferation, separated CTPS1 catalytic function from its structural polymerization role.

    Evidence Interaction assays under non-polymerizing conditions, enzymatic activity with CTP inhibition curves, H355A mutagenesis with proliferation readouts

    PMID:40957650

    Open questions at the time
    • Stoichiometry of CTPS1–CTPS2 heterocomplexes in different tissues unknown
    • Physiological contexts where cytoophidia confer a selective advantage remain undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the complete set of transcription factors driving CTPS1 induction upon immune activation, the precise SUMOylation sites and their regulation, the physiological function of cytoophidium assembly if it is dispensable for proliferation, and whether CTPS1-selective inhibitors can achieve therapeutic windows in clinical immunology and oncology settings.
  • No clinical trial data on CTPS1-selective inhibitors
  • Role of cytoophidia in metabolic regulation versus sequestration unresolved
  • Tissue-specific CTPS1/CTPS2 compensation map absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 5 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 2
Partners
CTPS2HSPD1IMPDH2INHBARASD2SMURF1YBX1
Complex memberships
CTPS1-CTPS2 heterocomplexcytoophidium (CTPS1/IMPDH2 filament)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Loss-of-function homozygous mutation in CTPS1 (rs145092287) in humans causes severe immunodeficiency characterized by impaired proliferation of activated T and B cells in response to antigen receptor-mediated activation. CTPS1 expression is low in resting T cells but rapidly upregulated following TCR activation. Normal T-cell proliferation was restored by expressing wild-type CTPS1 or by addition of exogenous CTP or cytidine, demonstrating that CTPS1 is specifically required to sustain CTP pools for lymphocyte proliferation during immune responses. Patient genetic analysis, lymphocyte proliferation assays, CTP pool measurements, complementation with wild-type CTPS1 and exogenous CTP/cytidine Nature High 24870241
1995 De novo CTP synthesis via CTP synthase activity is essential for the disproportionate expansion of pyrimidine nucleotide pools (CTP up to 8-fold) in proliferating T-lymphocytes; resting T-lymphocytes meet metabolic requirements by salvage, while intact de novo pathways are required for pool expansion upon activation. Azaserine (glutamine antagonist blocking CTPS activity) reduced pyrimidine pool expansion by 70%. HPLC-based nucleotide pool quantification in PHA-stimulated T-lymphocytes with pharmacological inhibitors (azaserine, ribavirin) and radiolabeled precursors The Journal of biological chemistry High 8530356
2011 CTPS1 (and IMPDH2) are the primary components of cytoplasmic rod and ring (RR) structures (cytoophidia) in mammalian cells. CTPS1 enzyme inhibitors (6-diazo-5-oxo-L-norleucine, Acivicin) induce RR formation in >95% of cells in a dose-dependent manner. RR structures are not enriched in actin, tubulin, or vimentin and are not associated with centrosomes, indicating they are a distinct cytoplasmic compartment formed in response to disturbances in the CTP synthetic pathway. Immunofluorescence with human autoantibodies, co-localization studies, pharmacological induction with CTPS inhibitors and IMPDH2 inhibitor, GFP-CTPS1 overexpression and IMPDH2 knockdown in HeLa cells PloS one High 22220215
2020 The CTPS1 T566Dfs26X mutant protein found in immunodeficient patients is hypomorphic, resulting in 80–90% reduction in protein expression and CTPS activity. The mutant retained normal enzymatic activity when expressed at levels comparable to wild-type CTPS1, indicating the loss-of-function is entirely attributable to protein instability rather than catalytic impairment. Inactivation of CTPS1 in a T-cell leukemia line fully abolished proliferation, and expression of the mutant failed to restore proliferation unless forced to wild-type expression levels. Immunophenotyping, T-cell proliferation assays, CTPS activity measurements, CTPS1 KO in leukemia cell lines, complementation with CTPS1 T566Dfs26X at varying expression levels JCI insight High 32161190
2021 Cryo-EM structures reveal that CTP regulates both CTPS1 and CTPS2 isoforms by binding in two inhibitory sites that clash with substrates (product feedback inhibition). CTPS1 is less sensitive to CTP feedback inhibition than CTPS2, consistent with its role in boosting CTP levels during lymphocyte proliferation. Small-molecule CTPS1-selective inhibitors mimic CTP binding at one inhibitory site; a single amino acid difference between isoforms explains isoform selectivity. These inhibitors bind CTPS1 assembled into large-scale filaments, which represent a hyperactive enzyme form, and both inhibit human primary T-cell proliferation. Cryo-EM structure determination, enzymatic activity assays with CTP dose-response, site-directed mutagenesis, small-molecule inhibitor characterization, primary T-cell proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 34583994
2018 IMPDH2 and CTPS1 cytoophidia can co-localize and interact via interfilament interaction within mixed cytoophidium structures in HeLa cells. Live-cell imaging and super-resolution confocal imaging showed IMPDH- and CTPS-based filaments align or intertwine, suggesting coordination between CTP and GTP biosynthetic pathways through cytoophidium interactions. Live-cell imaging, super-resolution confocal microscopy of HeLa cells co-expressing OFP-IMPDH2 and GFP-CTPS1; cytoophidium assembly/disassembly/movement tracking The FEBS journal Medium 30085408
2022 CTPS1 (but not CTPS2) inhibition selectively induces DNA replication stress in MYC-overexpressing cancer cells. MYC-driven rRNA synthesis causes selective replication stress upon CTPS inhibition. Combined inhibition of CTPS1 and ATR is synthetically lethal in MYC-overexpressing cells, promoting cell death in vitro and decreasing tumor growth in vivo. Cell viability assays, DNA replication stress markers, siRNA knockdown of CTPS1 vs CTPS2, ATR inhibitor combination, xenograft mouse models Cancer research High 35022212
2023 CTPS1 has higher intrinsic enzymatic activity than CTPS2 and is more resistant to inhibition by 3-deaza-uridine (a UTP analog). CTPS1 is the primary driver of cell proliferation; CTPS2 contribution is modest when CTPS1 is expressed but becomes essential in CTPS1-absent cells. This was confirmed across more than 1,000 cancer cell lines in public databases. CTPS1 and/or CTPS2 inactivation by gene editing, complementation experiments, in vitro enzymatic activity assays with 3-deaza-uridine inhibitor, analysis of public cancer cell line dependency databases Life science alliance High 37348953
2015 CTPS1 and IMPDH2 are the protein components of rod/ring (RR)/cytoophidium structures in mammalian cells; their co-assembly is cell-type dependent. In HeLa cells treated with DON, mixed IMPDH2/CTPS1 RR comprise ~31% of structures, while pure CTPS1-only and IMPDH2-only structures also form. Ribavirin and MPA treatment induced only IMPDH2-based RR, demonstrating pathway-specific assembly regulation. Immunofluorescence, pharmacological induction (DON, ribavirin, MPA) in HeLa and COS-7 cells, transfection with NHA-tagged CTPS1 constructs Journal of genetics and genomics Medium 26165495
2021 CTPS1 forms cytoophidia in zebrafish tissues under normal physiological conditions. A point mutation H355A in CTPS1a/1b abrogates cytoophidium assembly. DON treatment induces additional cytoophidia formation in some tissues, demonstrating that cytoophidium assembly is regulated by enzymatic inhibition. Expression of zebrafish CTPS1a/1b in cultured cells, site-directed mutagenesis (H355A), immunofluorescence in larval and adult fish tissues, pharmacological induction with DON Experimental cell research Medium 34129847
2021 CTPS cytoophidia are present in thymocytes at the DN3-to-early-DP developmental stage under normal physiological conditions. Cytoophidium-presenting cells undergo rapid proliferation and show higher levels of c-Myc, phospho-Akt, and PFK. Inhibition of glycolysis with 2-DG disrupts cytoophidium structures and impairs cell proliferation, linking cytoophidium formation to glycolytic metabolism and pre-TCR signaling-induced metabolic switch. Immunofluorescence of major mouse organs, flow cytometry, 2-DG glycolysis inhibition, correlation with c-Myc/pAkt/PFK expression Experimental cell research Medium 34022203
2021 CTPS interacts with ATP synthase (ATPS) to maintain ATP levels on Day 3 of decidualization, while on Day 6 it associates instead with mitochondrial stress protein STRESS-70, correlating with reduced ATP. CTPS subcellular localization shifts from cytoplasm on Day 3 to both cytoplasm and nucleus on Day 6 during in vitro decidualization. Downregulation of CTPS by DON or siRNA inhibited the decidualization process and the AMPK signaling pathway. Co-immunoprecipitation coupled with mass spectrometry (IP-MS), subcellular fractionation/immunofluorescence, siRNA knockdown, ATP content measurement, AMPK pathway analysis Journal of cellular physiology Medium 33576499
2023 CTPS1 inhibition by the selective inhibitor STP-B activates DNA damage response (DDR) pathways and induces double-strand DNA breaks accumulating in early S phase in multiple myeloma cells, causing S-phase arrest and apoptosis. Synergistic growth inhibition and early apoptosis result from combining CTPS1 inhibition with pharmacological inhibitors of ATR, CHEK1, or WEE1. CTPS1 knockout, selective CTPS1 inhibitor STP-B treatment, cell cycle analysis (flow cytometry), DNA damage markers (γH2AX), pharmacological combination studies with DDR inhibitors Leukemia Medium 37898670
2024 CTPS1 inhibition in mantle cell lymphoma (MCL) cells leads to early S-phase cell cycle arrest accompanied by inhibition of translation, including reduction of the anti-apoptotic protein MCL1. Synergistic cell death results from combining CTPS1 inhibition with the BCL2 inhibitor venetoclax, both in vitro and in vivo, providing a mechanism-based therapeutic combination. STP-B pharmacological inhibition, cell cycle analysis, protein translation assays, MCL1 protein expression, venetoclax combination in vitro and xenograft models Haematologica Medium 38385294
2024 CTPS1 cytoophidia are mainly stacked with tetramers as their minimum structural subunit. CTPS can act as the nucleation core to induce subsequent growth of P5CS (Δ1-pyrroline-5-carboxylate synthase) filaments. The direction of growth and extension differs between CTPS and P5CS self-assembly, as revealed by single-molecule fluorescence imaging of real-time assembly dynamics in vitro. Single-molecule fluorescence imaging, photobleach counting for stoichiometry, oligomer state distribution analysis under different conditions, co-assembly of CTPS and P5CS in vitro The journal of physical chemistry. B Medium 38236746
2024 RASD2 promotes SUMOylation and inhibits ubiquitination of CTPS1, thereby increasing CTPS1 protein stability and promoting endometriosis progression. Histone lactylation (H3K18la) promotes transcription of RASD2, which then stabilizes CTPS1 via this post-translational modification mechanism. IP-MS identification, Co-IP, ChIP-qPCR, Western blot for SUMOylation/ubiquitination, cell proliferation and migration assays, endometriosis mouse models American journal of physiology. Cell physiology Medium 39672102
2025 INHBA protein interacts with CTPS1 and competitively inhibits SMURF1 (SMAD Specific E3 Ubiquitin Protein Ligase 1)-mediated ubiquitination, thereby enhancing CTPS1 stability and promoting pyrimidine metabolism and gemcitabine resistance in pancreatic cancer cells. Immunoprecipitation mass spectrometry (IP-MS) to identify INHBA-CTPS1 interaction, Co-IP, ubiquitination assays, drug sensitivity analysis, xenograft models Cancer cell international Medium 41239468
2025 CTPS2 directly interacts with CTPS1 independently of polymerization/cytoophidium formation and modulates CTPS1 enzymatic activity: when CTPS1 is associated with CTPS2, its enzymatic activity is decreased and becomes more sensitive to CTP product feedback inhibition. CTPS2-containing filaments in cytoophidia are dependent on CTPS1 expression. CTPS1H355A and CTPS2H355A mutants unable to form cytoophidia still sustain normal cell proliferation, indicating cytoophidia are not required for proliferation per se. Co-localization studies, genetic inactivation/complementation, enzymatic activity assays with CTP inhibition curves, CTPS1/2 interaction assays independent of polymerization, H355A mutagenesis Life science alliance High 40957650
2025 CTPS1 upregulates CEPT1 (choline/ethanolamine phosphotransferase 1) expression by increasing CTP availability, thereby reprogramming glycerophospholipid metabolism. The resulting glycerophospholipids maintain mitochondrial homeostasis and promote BNIP3-mediated mitophagy, driving DLBCL progression. scRNA-seq, CTPS1 genetic manipulation, CEPT1 expression analysis, lipidomic profiling, mitophagy assays (BNIP3), CTPS1 inhibitor R80 Redox biology Medium 41865720
2025 CTP (the product of CTPS1) acts as a key regulator of hCTPS1 filamentation. Cryo-EM structures of CTP-bound hCTPS1 filaments reveal the molecular details of CTP binding and its role in filament assembly. CTP generated from the enzymatic reaction does not trigger filament disassembly. Two distinct CTP-binding pockets exist and the filamentation mechanism is evolutionarily conserved across eukaryotic CTPS. Cryo-EM structure determination of CTP-bound hCTPS1 filaments, biochemical filamentation assays, enzymatic product analysis bioRxivpreprint Medium
2022 YBX1 binds to the promoter of CTPS1 to promote its transcription. YBX1 overexpression-driven cell proliferation and invasion in triple-negative breast cancer cells is reversed by CTPS1 knockdown, placing CTPS1 downstream of YBX1 in a transcriptional axis. Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown, rescue experiments with YBX1 overexpression + CTPS1 knockdown Journal of translational medicine Medium 34991621
2025 HSPD1 (Hsp60) interacts with CTPS and promotes formation of CTPS cytoophidia in C2C12 cells. Interference with Hspd1 inhibits cytoophidium formation even with CTPS overexpression. CTPS H355A mutation prevents cytoophidium formation and inhibits C2C12 cell viability and proliferation, whereas CTPS overexpression promotes cytoophidium formation and increases proliferation. Co-immunoprecipitation to detect HSPD1-CTPS interaction, siRNA knockdown of Hspd1, CTPS overexpression and H355A mutagenesis, EdU proliferation assay, CCK-8 viability assay Experimental cell research Medium 39971178

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Current biology : CB 386 15324660
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
1995 Importance of ribonucleotide availability to proliferating T-lymphocytes from healthy humans. Disproportionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitors. The Journal of biological chemistry 278 8530356
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2018 K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains. Proceedings of the National Academy of Sciences of the United States of America 227 29378950
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2012 Functional genomics identifies therapeutic targets for MYC-driven cancer. Proceedings of the National Academy of Sciences of the United States of America 203 22623531
2004 Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. The Journal of biological chemistry 185 15161933
2014 CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature 178 24870241
2011 Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells. PloS one 170 22220215
1991 Chromosome mapping of the human cytidine-5'-triphosphate synthetase (CTPS) gene to band 1p34.1-p34.3 by fluorescence in situ hybridization. Human genetics 124 1959918
2018 Interfilament interaction between IMPDH and CTPS cytoophidia. The FEBS journal 53 30085408
2022 CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1. Journal of translational medicine 45 34991621
2015 Assembly of IMPDH2-based, CTPS-based, and mixed rod/ring structures is dependent on cell type and conditions of induction. Journal of genetics and genomics = Yi chuan xue bao 45 26165495
2022 Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells. Cancer research 44 35022212
2020 Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation. JCI insight 36 32161190
2021 Structural basis for isoform-specific inhibition of human CTPS1. Proceedings of the National Academy of Sciences of the United States of America 32 34583994
2021 CTPS and IMPDH form cytoophidia in developmental thymocytes. Experimental cell research 22 34022203
2021 CTPS forms the cytoophidium in zebrafish. Experimental cell research 20 34129847
2023 Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferation. Life science alliance 19 37348953
2023 CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1. Leukemia 18 37898670
2022 CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells. Cell cycle (Georgetown, Tex.) 13 35912542
1991 Genomic organization and chromosomal localization of the human CTP synthetase gene (CTPS). Genomics 13 1783378
2023 Fat body-specific reduction of CTPS alleviates HFD-induced obesity. eLife 11 37695169
2021 ASNS disruption shortens CTPS cytoophidia in Saccharomyces cerevisiae. G3 (Bethesda, Md.) 8 33561249
2021 Energy deficiency caused by CTPS downregulation in decidua may contribute to pre-eclampsia by impairing decidualization. Journal of cellular physiology 8 33576499
2024 Selective pharmacologic targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma. Haematologica 5 38385294
2024 Single-Molecule Fluorescence Imaging Reveals Coassembly of CTPS and P5CS. The journal of physical chemistry. B 3 38236746
2024 Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1. American journal of physiology. Cell physiology 2 39672102
2022 CTPS cytoophidia formation affects cell cycle progression and promotes TSN‑induced apoptosis of MKN45 cells. Molecular medicine reports 2 36043523
2025 CTPS cytoophidia in Drosophila: distribution, regulation, and physiological roles. Experimental cell research 1 40122502
2022 [Interference of CTPS gene promotes toosendanin-induced apoptosis of human gastric cancer MKN-45 cells]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 36073210
2022 Asymmetric inheritance of cytoophidia could contribute to determine cell fate and plasticity: The onset of alternative differentiation patterns in daughter cells may rely on the acquisition of either CTPS or IMPDH cytoophidia: The onset of alternative differentiation patterns in daughter cells may rely on the acquisition of either CTPS or IMPDH cytoophidia. BioEssays : news and reviews in molecular, cellular and developmental biology 1 36209393
2020 [Effects of Toosendanin on the formation of CTPS cytoophidium in human gastric cancer cell MKN-45 and its mechanism]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 1 33719272
2026 CTPS1 modulates mitophagy to propel diffuse large B-cell lymphoma via reshaping CEPT1-mediated phospholipid metabolism. Redox biology 0 41865720
2025 HSPD1-facilitated formation of CTPS cytoophidia promotes proliferation in C2C12 cells. Experimental cell research 0 39971178
2025 Integrative role of CTPS cytoophidia in polyploid tissue growth and nutrient adaptation. Insect science 0 40287929
2025 [Circ_0000437 promotes proliferation, invasion, migration and epithelial-mesenchymal transition of breast cancer cells by targeting the let-7b-5p/CTPS1 axis]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 40916530
2025 CTPS2 regulates CTP synthetase activity by interacting with CTPS1. Life science alliance 0 40957650
2025 VitisC: Visualizing small proteins via the integrated scaffold of Escherichia coli CTP synthase (CTPS) cytoophidium. International journal of biological macromolecules 0 41101423
2025 INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism. Cancer cell international 0 41239468
2024 MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1. Experimental cell research 0 39197579
2024 Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells. HemaSphere 0 39380841