- Length
- 2225 aa
- Mass
- 243.0 kDa
- Annotated
- 2026-04-28
130 papers in source corpus
32 papers cited in narrative
32 extracted findings
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
Insufficient on-target evidence to synthesize a narrative — discovery timeline does not match the canonical CAD protein.
Mechanism profile
Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.
Evidence
Reading pass · 32 per-paper findings extracted from the source corpus
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1982 | The CAD gene (encoding carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, and dihydroorotase) was localized by in situ hybridization to the short arm of Syrian hamster chromosome B9; amplification of this gene underlies resistance to PALA (N-phosphonacetyl-L-aspartate), an inhibitor of its aspartate transcarbamylase activity. | In situ hybridization with radiolabeled CAD probes on metaphase chromosomes from wild-type and PALA-resistant cell lines | Molecular and cellular biology | High | 6180304 |
| 1981 | A functional CAD gene was cloned from Syrian hamster cells; introduction into CAD-deficient CHO cells by protoplast fusion rescued pyrimidine biosynthesis and conferred PALA resistance, demonstrating that the CAD gene encodes all three enzymatic activities (CPS, ATCase, DHOase) necessary for de novo UMP synthesis. | Cosmid cloning, protoplast fusion into CAD-deficient CHO cells, complementation assay with PALA selection | Cell | High | 6277500 |
| 1982 | The CAD gene spans ~25 kb and contains ~37 intervening sequences encoding a 7.9 kb mRNA; the coding sequences are small (100–400 bp) and the gene encodes the first three steps of UMP biosynthesis as a single polypeptide. | Electron microscopy of R-loops, hybridization mapping of genomic clones from amplified CAD cell lines | Molecular and cellular biology | High | 6125880 |
| 1983 | The aspartate transcarbamylase (ATCase) activity of CAD resides in a discrete ~40 kDa domain released by controlled proteolysis; the isolated domain forms a 2–3 subunit oligomer with Km for aspartate of 21 mM and turnover of 4,780 min⁻¹, similar to intact CAD, but with reduced stability, indicating that interactions with other CAD domains stabilize the ATCase domain. | Controlled proteolysis of CAD, purification of the 40 kDa ATCase fragment, kinetic analysis, sedimentation studies | The Journal of biological chemistry | High | 6300078 |
| 1986 | The dihydroorotase (DHOase) domain of CAD is a ~44 kDa N-terminal fragment released by elastase cleavage; it contains one tightly bound zinc atom essential for catalysis, exists as a homodimer in solution, and the amino terminus of DHOase is identical to that of intact CAD, establishing the domain order as DHO-CPS-ATC. | Controlled elastase proteolysis, purification of DHOase domain, atomic absorption spectrophotometry for zinc, isotopic labeling with ⁶⁵Zn, hydrodynamic analysis (sedimentation, diffusion coefficients), immunoblotting | The Journal of biological chemistry | High | 2871022 |
| 1986 | CAD gene amplification in single-step PALA-resistant cells involves co-amplification of the CAD gene and at least 65 kb of flanking DNA, with very few novel chromosomal joints, suggesting very large amplicons (~10,000 kb per CAD gene copy) rather than small circular units. | Probing with recombinant phage and cosmids spanning 380 kb of amplified DNA in 33 independent cell lines; Southern blotting for novel joints | The EMBO journal | High | 3023056 |
| 1985 | CAD RNA accumulates at equal levels in nucleus and cytoplasm of Syrian hamster cells; nuclear CAD RNA is found in a large ~200S ribonucleoprotein particle distinct from 30S RNP particles, with no detectable higher-molecular-weight precursor forms. | In situ hybridization, subcellular fractionation, sucrose gradient sedimentation, solution and blot hybridization | Molecular and cellular biology | Medium | 3990684 |
| 1987 | CAD gene transcription is rapidly shut off (within 4 hours) during terminal differentiation of HL-60 promyelocytes induced by TPA or retinoic acid/dbcAMP, as demonstrated by nuclear run-off assays, with corresponding loss of CAD mRNA; the CAD protein has a half-life of ~24 hours in differentiating cells. | Nuclear run-off transcription assays, RNA blotting, aspartate transcarbamylase activity assays during HL-60 differentiation | Molecular and cellular biology | High | 2885743 |
| 1988 | Domain mapping by limited proteolysis and antibody probing established the domain order in CAD as GLNase-CPSase-DHOase-ATCase; phosphorylation by cAMP-dependent protein kinase occurs at two sites, with site 1 located at the C-terminal end of the CPSase domain (GLNase/CPSase region), and phosphorylation accelerates proteolytic cleavage and abolishes the protective effect of UTP. | Limited proteolysis with elastase and trypsin, SDS-PAGE, Western blotting with domain-specific antibodies, ³²P-labeling and tryptic peptide mapping with isoelectric focusing | European journal of biochemistry | High | 3345746 |
| 1988 | CAD is localized predominantly in the cytoplasmic compartment of mammalian cells, excluded from the nucleus, and exhibits a punctate staining pattern suggesting association with subcellular organelles; it is not concentrated near mitochondria, indicating that the DHOase product dihydroorotate diffuses through cytosol rather than being channeled to mitochondrial dihydroorotate dehydrogenase. | Differential centrifugation, immunofluorescence cytochemistry, immunoperoxidase staining in BHK cells and CAD-overproducing BHK 165-23 cells | FASEB journal | Medium | 2903106 |
| 1995 | An origin of bidirectional DNA replication (OBR) resides within the constitutively expressed CAD transcriptional unit, localized to a 5 kb region near the gene's center; this OBR functions in both single-copy and amplified CAD loci in Syrian and Chinese hamster cells, demonstrating conservation of origin recognition machinery across species. | Nascent strand abundance assay, two-dimensional gel electrophoresis of replication intermediates, analysis of CAD episomes and chromosomally integrated sequences | Molecular and cellular biology | High | 7623808 |
| 1997 | Myc-Max, but not USF, binding to the E box at +65 of the CAD promoter is essential for G1/S-phase transcriptional activation of CAD; mutations in nucleotides flanking the E box that selectively reduce Myc-Max binding abolish growth-regulated CAD induction without affecting USF binding. | In vivo UV cross-linking and immunoprecipitation (ChIP precursor), promoter mutagenesis with reporter assays, growth synchronization experiments | Molecular and cellular biology | High | 9111322 |
| 2001 | c-Myc activates transcription of the cad gene by a post-RNA polymerase II recruitment mechanism: RNA Pol II is pre-loaded at the cad promoter in quiescent cells, and c-Myc stimulates CTD hyperphosphorylation (promoter clearance/elongation) by recruiting P-TEFb (cdk9/cyclin T1); direct recruitment of cyclin T1 to the promoter substitutes for c-Myc. | Chromatin immunoprecipitation (ChIP) with antibodies to Pol II CTD (unphosphorylated and hyperphosphorylated), co-immunoprecipitation of c-Myc transactivation domain with cdk9/cyclin T1, activator bypass experiments with Gal4-cyclin T1 | The Journal of biological chemistry | High | 11673469 |
| 2001 | High rates of CAD gene amplification (50–100-fold elevated) occur in human cell lines deficient in MLH1 or MSH6 mismatch repair proteins; FISH analysis indicates amplification arises from unequal sister chromatid exchanges and translocations involving chromosome 2, implicating MutSα and MutLα in suppression of gene amplification. | PALA-resistance selection for CAD gene amplification, fluorescence in situ hybridization (FISH), comparison across mismatch repair-deficient vs. proficient cell lines | Proceedings of the National Academy of Sciences of the United States of America | High | 11717437 |
| 2003 | The mSin3A/HDAC2 corepressor complex, together with PRMT5 and Brg1-based hSWI/SNF complexes, is directly recruited to the cad promoter to mediate transcriptional repression; PRMT5 preferentially methylates hypoacetylated histones H3 and H4; inactivation of Brg1 or treatment with HDAC inhibitor depsipeptide alters cad repression. | Chromatin immunoprecipitation (ChIP) for Brg1, mSin3A, HDAC2, PRMT5 at cad promoter; histone methylation assays with acetylated vs. hypoacetylated histones; protein-protein interaction studies; reporter assays in cells expressing dominant-negative Brg1 | Molecular and cellular biology | High | 14559996 |
| 1988 | Chromosome aberrations (including dicentrics at high frequency in hyperdiploid/polyploid cells containing two copies of the marker chromosome) are associated with CAD gene amplification in Chinese hamster V79 cells; amplified CAD sequences reside in the terminal region of a marker chromosome with elongated q arms (homogeneously staining region). | In situ hybridization with CAD DNA probe, G-banding, cytogenetic analysis of 11 PALA-resistant sublines | Mutation research | Medium | 2896299 |
| 2005 | HIF-1α directly binds to a hypoxia response element (HRE) in the cad promoter and transcriptionally represses CAD expression under hypoxia or DFO-induced HIF-1α accumulation; this is demonstrated by promoter-reporter assays with wild-type and mutant HRE constructs and by ChIP showing HIF-1α occupancy at the cad promoter in vivo. | Promoter-reporter assays (luciferase) with HRE deletion/mutation constructs, overexpression of wild-type and dominant-negative HIF-1α, chromatin immunoprecipitation (ChIP) for HIF-1α at cad promoter, RT-PCR of CAD expression under hypoxia | Nucleic acids research | High | 16155188 |
| 2011 | CAD physically interacts with the androgen receptor (AR) in prostate tumor cells and promotes AR nuclear translocation and transcriptional activity; higher CAD mRNA levels in radical prostatectomy specimens correlate with local tumor extension and cancer relapse. | Immunopurification of AR partners from human tumor xenografts followed by mass spectrometry; co-immunoprecipitation and nuclear translocation assays in C4-2, LNCaP, 22RV1, and PC3 cells; luciferase reporter for AR transcriptional activity | FASEB journal | Medium | 21982950 |
| 2012 | CAD physically interacts with NOD2 (identified by immunoprecipitation-coupled mass spectrometry) and acts as a negative regulator of NOD2-dependent NF-κB and p38 MAPK activation and intracellular bacterial killing; CAD overexpression inhibits NOD2 signaling while CAD knockdown or pharmacological inhibition enhances NOD2-dependent antibacterial function. | Immunoprecipitation-coupled mass spectrometry (Co-IP/MS), co-immunoprecipitation in HCT116 cells, NF-κB and p38 reporter assays, Salmonella gentamicin protection assays, siRNA knockdown, CAD inhibitor treatment | Gastroenterology | High | 22387394 |
| 2014 | In zebrafish, loss-of-function of cad (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase) causes reduced Notch signaling and hyperbranching arteries due to increased endothelial responsiveness to Vegfc/Vegfr3; genetic epistasis places cad upstream of Notch signaling in the regulation of angiogenesis, with CAD's role linked to UDP biosynthesis required for protein glycosylation (a prerequisite for Notch signaling). | Forward genetic screen, positional cloning, Notch reporter transgene assay, genetic epistasis with Vegfc/Vegfr3 pathway mutants, morpholino knockdown | Developmental dynamics | Medium | 25294789 |
| 2019 | CAD is a 1.5 MDa particle formed by hexameric association of a 250 kDa polypeptide carrying three enzymatic activities (CPS, ATCase, DHOase); the ATCase domain mediates hexameric and trimeric self-assembly; the fusion of the first three pyrimidine biosynthetic activities into a single multienzymatic particle is unique to animals. | Biochemical and structural characterization review synthesizing limited proteolysis, hydrodynamic studies, electron microscopy, and domain expression data | Sub-cellular biochemistry | Medium | 31939163 |
| 2020 | CAD directly interacts with Ebola virus nucleoprotein NP via the glutaminase (GLN) domain of CAD; NP recruits CAD into viral inclusion bodies, and CAD is required for both viral genome replication and transcription, functioning through its pyrimidine synthesis activity (substrate rescue with uridine/cytidine partially restores viral replication upon CAD knockdown). | siRNA knockdown, co-immunoprecipitation of NP with CAD, co-immunofluorescence colocalization assays, reverse genetics life cycle modelling systems, substrate rescue experiments with uridine/cytidine | Cells | High | 32370067 |
| 2020 | A CRISPR/Cas9-generated human CAD-knockout cell line requires uridine for survival; transient transfection with recombinant CAD restores growth in uridine-free medium, enabling a quantitative complementation assay to assess pathogenicity of CAD missense variants; 16 of 34 tested variants were identified as deleterious, confirming CAD deficiency as a uridine-responsive inborn metabolic disorder. | CRISPR/Cas9 knockout of CAD, complementation assay by transient transfection of variant CAD constructs, growth assay in uridine-depleted medium | Genetics in medicine | High | 32461667 |
| 2021 | Afatinib, an EGFR tyrosine kinase inhibitor, directly targets CAD and suppresses CD8+ T lymphocyte proliferation by inhibiting de novo pyrimidine biosynthesis; afatinib reduces tumor-infiltrating lymphocyte numbers in mouse tumor models, and sequential (but not simultaneous) combination with anti-PD1 therapy enhances efficacy. | Kinase inhibitor profiling identifying CAD as afatinib target, CD8+ T cell proliferation assays with/without afatinib and CAD inhibitors, flow cytometry of tumor-infiltrating lymphocytes in LLC-bearing mice, combination therapy experiments in MC38 and LLC models | Cancer research | Medium | 33771897 |
| 2021 | CAD is a 1.5 MDa hexamer; the dihydroorotase (DHO) domain forms homodimers in solution and crystallizes in space group C222(1) diffracting to 1.75 Å resolution; the ATCase domain forms homotrimers and mediates hexamer formation of intact CAD. | Recombinant expression and purification of CAD DHO and ATCase domains, size exclusion chromatography, X-ray crystallography (synchrotron data collection) | Protein science | High | 34288185 |
| 2012 | The dihydroorotase (DHO) domain of human CAD forms homodimers in solution and yields crystals diffracting to 1.75 Å; X-ray data indicate one molecule per asymmetric unit, providing the first structural data on the isolated DHO domain of human CAD. | Recombinant expression in insect cells, purification, size exclusion chromatography, X-ray crystallography at SLS synchrotron | Acta crystallographica. Section F | Medium | 23143245 |
| 2013 | The ATCase domain of human CAD forms homotrimers in solution; it crystallizes in space group P6(3)22 (or pseudo-P21 with twinning) and diffracts to 2.1 Å, providing the first structural data on a eukaryotic ATCase and confirming that ATCase-ATCase interactions mediate hexamerization of the full CAD complex. | Recombinant expression in bacteria, purification, size exclusion chromatography, X-ray crystallography with PALA inhibitor, synchrotron data collection | Acta crystallographica. Section F | Medium | 24316846 |
| 2022 | Oncogenic β-catenin transcriptionally upregulates AKT2, which then phosphorylates CAD at S1406 and S1859 to activate de novo pyrimidine synthesis; this β-catenin/AKT2/CAD signaling axis is the major metabolic aberration in β-catenin mutant liver cancer, and its inhibition preferentially suppresses proliferation of β-catenin mutant cells. | Untargeted metabolomics in β-catenin mutant cell lines and mouse livers, phosphorylation site mapping by mass spectrometry, site-directed mutagenesis of S1406 and S1859 in CAD, mouse liver tumor models, pharmacological inhibition of the pathway | Proceedings of the National Academy of Sciences of the United States of America | High | 36122209 |
| 2022 | CAD is rapidly phosphorylated upon naïve CD8+ T cell activation in an mTORC1-dependent manner and remains phosphorylated in memory T cells; persistent CAD activity drives ongoing de novo pyrimidine synthesis that supports ribosomal RNA synthesis and ribosomal biogenesis required for the rapid recall response; CAD inhibition reduces pre-rRNA levels and ribosomal protein abundance without affecting cytokine mRNA. | Cell synchronization and metabolomics, mTORC1 inhibition (rapamycin), CAD inhibitor treatment, CAD overexpression, pre-rRNA quantification, flow cytometry of cytokine production, measurement of ribosomal protein levels | Science immunology | High | 35622902 |
| 2023 | CAD activity is allosterically regulated during the cell cycle via two Animalia-specific loops in the allosteric domain that sense and bind UTP (an allosteric inhibitor); a signal transmission loop (homologous to one in mitochondrial CPS) regulates formation of a substrate channel controlling CAD activity; this allosteric mechanism accounts for cell cycle phase-dependent changes in de novo pyrimidine synthesis. | Cell synchronization and metabolomics to identify cell cycle phase-dependent metabolites, systematic mutational scanning of allosteric domain, structural modelling based on CPS homology, UTP binding assays | Nature metabolism | High | 36747088 |
| 2023 | Atomic-resolution crystal structures of eight pathogenic missense variants in the CAD dihydroorotase (DHO) domain reveal that pathogenic variants cluster in the DHO domain and impair CAD activity, stability, or dimerization; molecular dynamics analysis confirms conformational effects of damaging variants; combined functional and structural analysis enables reliable reclassification of CAD variants. | Growth complementation assay in CRISPR CAD-knockout cells, X-ray crystallography of DHO domain variants, molecular dynamics simulations, functional kinetic assays | Journal of inherited metabolic disease | High | 37540500 |
| 2019 | A missense mutation p.Tyr452Cys in the carbamoyl-phosphate synthetase 2 domain of CAD, affecting a perfectly conserved tyrosine, causes recessive embryonic lethality in cattle (French Normande breed) with nearly complete penetrance, demonstrating that CAD enzymatic activity is essential for viability during embryonic development. | Genome-wide SNP scanning for homozygous haplotype deficiency in 77,815 cattle, fine mapping and whole-genome sequencing, Sanger sequencing, large-scale genotyping of 33,323 Normande animals | Journal of dairy science | Medium | 31056337 |
Source papers
Stage 0 corpus · 130 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 |
| 2006 | A probability-based approach for high-throughput protein phosphorylation analysis and site localization. | Nature biotechnology | 1336 | 16964243 |
| 2015 | A human interactome in three quantitative dimensions organized by stoichiometries and abundances. | Cell | 1015 | 26496610 |
| 2004 | A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. | Nature cell biology | 841 | 14743216 |
| 2018 | VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. | Cell discovery | 829 | 29507755 |
| 2008 | Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. | Cell | 787 | 18854154 |
| 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 |
| 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 |
| 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 |
| 2015 | Aerobic glycolysis tunes YAP/TAZ transcriptional activity. | The EMBO journal | 362 | 25796446 |
| 2011 | Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. | Cancer cell | 356 | 21575865 |
| 2021 | A proximity-dependent biotinylation map of a human cell. | Nature | 339 | 34079125 |
| 2010 | Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. | Cell | 318 | 21145461 |
| 2011 | A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. | Nature | 269 | 21654808 |
| 2013 | The functional interactome landscape of the human histone deacetylase family. | Molecular systems biology | 235 | 23752268 |
| 2010 | MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. | Immunology and cell biology | 221 | 20458337 |
| 2015 | La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). | The Journal of biological chemistry | 213 | 25940091 |
| 2015 | ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. | Nature | 209 | 26618866 |
| 2018 | An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. | Nature communications | 201 | 29568061 |
| 2003 | mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad. | Molecular and cellular biology | 201 | 14559996 |
| 2004 | Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. | The Journal of biological chemistry | 185 | 15161933 |
| 2005 | WW domains provide a platform for the assembly of multiprotein networks. | Molecular and cellular biology | 184 | 16055720 |
| 2017 | The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs. | Nature communications | 176 | 28685749 |
| 2013 | Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. | Nature methods | 170 | 23455922 |
| 2005 | Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. | Journal of cellular biochemistry | 165 | 15723341 |
| 2001 | c-Myc mediates activation of the cad promoter via a post-RNA polymerase II recruitment mechanism. | The Journal of biological chemistry | 162 | 11673469 |
| 1997 | Myc versus USF: discrimination at the cad gene is determined by core promoter elements. | Molecular and cellular biology | 145 | 9111322 |
| 2001 | Computer-aided design (CAD) of Mn(II) complexes: superoxide dismutase mimetics with catalytic activity exceeding the native enzyme. | Inorganic chemistry | 101 | 11312732 |
| 2013 | Rapid quantification of yeast lipid using microwave-assisted total lipid extraction and HPLC-CAD. | Analytical chemistry | 90 | 23634639 |
| 2004 | Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway. | Molecular cell | 89 | 15149602 |
| 2001 | CAD/DFF40 nuclease is dispensable for high molecular weight DNA cleavage and stage I chromatin condensation in apoptosis. | The Journal of biological chemistry | 87 | 11577114 |
| 1982 | Single-copy and amplified CAD genes in Syrian hamster chromosomes localized by a highly sensitive method for in situ hybridization. | Molecular and cellular biology | 87 | 6180304 |
| 2008 | Cloning and functional characterization of the cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus. | Applied microbiology and biotechnology | 84 | 18584171 |
| 2014 | Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis. | Atherosclerosis | 82 | 25461734 |
| 2000 | The DFF40/CAD endonuclease and its role in apoptosis. | Acta biochimica Polonica | 82 | 11996094 |
| 2013 | Identification of CAD candidate genes in GWAS loci and their expression in vascular cells. | Journal of lipid research | 81 | 23667179 |
| 2007 | The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. | The EMBO journal | 77 | 18007590 |
| 2000 | DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. | Current biology : CB | 75 | 10959840 |
| 2005 | Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. | Nucleic acids research | 73 | 16155188 |
| 1986 | The dihydroorotase domain of the multifunctional protein CAD. Subunit structure, zinc content, and kinetics. | The Journal of biological chemistry | 72 | 2871022 |
| 1986 | Structure of DNA formed in the first step of CAD gene amplification. | The EMBO journal | 72 | 3023056 |
| 2011 | OsCAD2 is the major CAD gene responsible for monolignol biosynthesis in rice culm. | Plant cell reports | 71 | 21912859 |
| 1981 | The cloning and reintroduction into animal cells of a functional CAD gene, a dominant amplifiable genetic marker. | Cell | 69 | 6277500 |
| 2012 | DeviceEditor visual biological CAD canvas. | Journal of biological engineering | 68 | 22373390 |
| 1982 | Structure of the gene for CAD, the multifunctional protein that initiates UMP synthesis in Syrian hamster cells. | Molecular and cellular biology | 68 | 6125880 |
| 2021 | Pyrimidine Biosynthetic Enzyme CAD: Its Function, Regulation, and Diagnostic Potential. | International journal of molecular sciences | 65 | 34638594 |
| 2015 | Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer. | British journal of cancer | 64 | 26633560 |
| 2008 | Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest). | Annals of human genetics | 64 | 18505420 |
| 2006 | Granzyme M directly cleaves inhibitor of caspase-activated DNase (CAD) to unleash CAD leading to DNA fragmentation. | Journal of immunology (Baltimore, Md. : 1950) | 60 | 16818775 |
| 2006 | T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking. | BMC medical genetics | 59 | 16620396 |
| 1985 | Abundant nuclear ribonucleoprotein form of CAD RNA. | Molecular and cellular biology | 55 | 3990684 |
| 2013 | The expanding roles of the Sd(a)/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2. | Biochimica et biophysica acta | 50 | 24112972 |
| 2001 | Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus. | Journal of neurochemistry | 50 | 11752060 |
| 1983 | The isolation and characterization of the aspartate transcarbamylase domain of the multifunctional protein, CAD. | The Journal of biological chemistry | 50 | 6300078 |
| 2018 | Low-cost, self-made CAD/CAM-guiding system for mandibular reconstruction. | Surgical oncology | 41 | 29937172 |
| 2009 | Genetic and environmental influences on total plasma homocysteine and coronary artery disease (CAD) risk among South Indians. | Clinica chimica acta; international journal of clinical chemistry | 41 | 19394322 |
| 2003 | Expression of caspase-activated deoxyribonuclease (CAD) and caspase 3 (CPP32) in the cochlea of cisplatin (CDDP)-treated guinea pigs. | Auris, nasus, larynx | 41 | 12927282 |
| 2001 | Ionic and cofactor requirements for the activity of the apoptotic endonuclease DFF40/CAD. | Molecular and cellular biochemistry | 41 | 11330826 |
| 1995 | Identification of an origin of bidirectional DNA replication in the ubiquitously expressed mammalian CAD gene. | Molecular and cellular biology | 41 | 7623808 |
| 2001 | High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6. | Proceedings of the National Academy of Sciences of the United States of America | 40 | 11717437 |
| 2019 | CAD, A Multienzymatic Protein at the Head of de Novo Pyrimidine Biosynthesis. | Sub-cellular biochemistry | 39 | 31939163 |
| 2010 | Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium. | Cardiovascular drugs and therapy | 39 | 20577898 |
| 2003 | Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities. | The Journal of cell biology | 39 | 14557248 |
| 2019 | Biocompatibility of Polymer and Ceramic CAD/CAM Materials with Human Gingival Fibroblasts (HGFs). | Polymers | 38 | 31484458 |
| 1988 | Mapping of catalytic domains and phosphorylation sites in the multifunctional pyrimidine-biosynthetic protein CAD. | European journal of biochemistry | 38 | 3345746 |
| 2017 | An HPLC-CAD/fluorescence lipidomics platform using fluorescent fatty acids as metabolic tracers. | Journal of lipid research | 35 | 28280113 |
| 2022 | Oncogenic β-catenin stimulation of AKT2-CAD-mediated pyrimidine synthesis is targetable vulnerability in liver cancer. | Proceedings of the National Academy of Sciences of the United States of America | 34 | 36122209 |
| 2010 | Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT. | Atherosclerosis | 34 | 20466371 |
| 2021 | Deciphering CAD: Structure and function of a mega-enzymatic pyrimidine factory in health and disease. | Protein science : a publication of the Protein Society | 33 | 34288185 |
| 2017 | Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine. | Cell death & disease | 33 | 28981092 |
| 2017 | Tracking a CAD-ALK gene rearrangement in urine and blood of a colorectal cancer patient treated with an ALK inhibitor. | Annals of oncology : official journal of the European Society for Medical Oncology | 32 | 28368455 |
| 2013 | TLR3 and TLR4 as potential clinically biomarkers of cardiovascular risk in coronary artery disease (CAD) patients. | Heart and vessels | 32 | 24146036 |
| 2000 | Structure of the CAD domain of caspase-activated DNase and interaction with the CAD domain of its inhibitor. | Journal of molecular biology | 31 | 10764577 |
| 2020 | Bio-mechanical characterization of a CAD/CAM PMMA resin for digital removable prostheses. | Dental materials : official publication of the Academy of Dental Materials | 30 | 33257084 |
| 2001 | Enzymatic active site of caspase-activated DNase (CAD) and its inhibition by inhibitor of CAD. | Archives of biochemistry and biophysics | 30 | 11361146 |
| 2021 | Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD. | Cancer research | 29 | 33771897 |
| 2012 | The nucleotide synthesis enzyme CAD inhibits NOD2 antibacterial function in human intestinal epithelial cells. | Gastroenterology | 28 | 22387394 |
| 2018 | The Sda and Cad glycan antigens and their glycosyltransferase, β1,4GalNAcT-II, in xenotransplantation. | Xenotransplantation | 27 | 29430727 |
| 1999 | Structure and promoter analysis of murine CAD and ICAD genes. | Cell death and differentiation | 27 | 10467348 |
| 2023 | Allosteric regulation of CAD modulates de novo pyrimidine synthesis during the cell cycle. | Nature metabolism | 26 | 36747088 |
| 2023 | The Effects of Thermocycling on the Physical Properties and Biocompatibilities of Various CAD/CAM Restorative Materials. | Pharmaceutics | 26 | 37631336 |
| 2013 | It takes a CAD to kill a tumor cell with a LMP. | Cancer cell | 26 | 24029224 |
| 2012 | PINK1 overexpression protects against C2-ceramide-induced CAD cell death through the PI3K/AKT pathway. | Journal of molecular neuroscience : MN | 26 | 22212487 |
| 2015 | Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM). | Diabetes/metabolism research and reviews | 24 | 25470794 |
| 2014 | Manipulating cinnamyl alcohol dehydrogenase (CAD) expression in flax affects fibre composition and properties. | BMC plant biology | 24 | 24552628 |
| 2007 | Studies of the central nervous system-derived CAD cell line, a suitable model for intraneuronal transport studies? | Journal of neuroscience research | 24 | 17335077 |
| 2022 | Fibrotic Signaling in Cardiac Fibroblasts and Vascular Smooth Muscle Cells: The Dual Roles of Fibrosis in HFpEF and CAD. | Cells | 23 | 35626694 |
| 2020 | Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy. | Genetics in medicine : official journal of the American College of Medical Genetics | 23 | 32461667 |
| 2021 | The Connection between Czc and Cad Systems Involved in Cadmium Resistance in Pseudomonas putida. | International journal of molecular sciences | 22 | 34575861 |
| 2020 | The Cellular Protein CAD is Recruited into Ebola Virus Inclusion Bodies by the Nucleoprotein NP to Facilitate Genome Replication and Transcription. | Cells | 22 | 32370067 |
| 2019 | A missense mutation (p.Tyr452Cys) in the CAD gene compromises reproductive success in French Normande cattle. | Journal of dairy science | 22 | 31056337 |
| 2014 | Genetic analysis of the 9p21.3 CAD risk locus in Asian Indians. | Thrombosis and haemostasis | 21 | 24452806 |
| 2001 | T-cell antigen discovery (T-CAD) assay: a novel technique for identifying T cell epitopes. | Journal of immunological methods | 21 | 11516759 |
| 2016 | An intrinsic DFF40/CAD endonuclease deficiency impairs oligonucleosomal DNA hydrolysis during caspase-dependent cell death: a common trait in human glioblastoma cells. | Neuro-oncology | 20 | 26755073 |
| 2005 | Polymorphisms in APOA1 and LPL genes are statistically independently associated with fasting TG in men with CAD. | European journal of human genetics : EJHG | 20 | 15657615 |
| 2001 | Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and the incidence of CAD. | American journal of cardiovascular drugs : drugs, devices, and other interventions | 20 | 14728017 |
| 1988 | Intracellular location of the multidomain protein CAD in mammalian cells. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 20 | 2903106 |
| 2020 | Response of two gingival cell lines to CAD/CAM composite blocks. | Dental materials : official publication of the Academy of Dental Materials | 19 | 32561116 |
| 2020 | The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial. | ARYA atherosclerosis | 19 | 33447259 |
| 2012 | IL-6 gene polymorphisms and CAD risk: a meta-analysis. | Molecular biology reports | 19 | 23242654 |
| 2021 | The Art of Designing DNA Nanostructures with CAD Software. | Molecules (Basel, Switzerland) | 18 | 33920889 |
| 2011 | Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 18 | 21982950 |
| 2008 | The major apoptotic endonuclease DFF40/CAD is a deoxyribose-specific and double-strand-specific enzyme. | Apoptosis : an international journal on programmed cell death | 18 | 18283539 |
| 2005 | Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF. | Biochemical and biophysical research communications | 18 | 16105646 |
| 2021 | Computational Analysis of Gly482Ser Single-Nucleotide Polymorphism in PPARGC1A Gene Associated with CAD, NAFLD, T2DM, Obesity, Hypertension, and Metabolic Diseases. | PPAR research | 17 | 34394332 |
| 2021 | Clinical effects with customized brackets and CAD/CAM technology: a prospective controlled study. | Progress in orthodontics | 17 | 34866163 |
| 2019 | Prediction and management of CAD risk based on genetic stratification. | Trends in cardiovascular medicine | 16 | 31543237 |
| 2010 | Methadone induces CAD degradation and AIF-mediated necrotic-like cell death in neuroblastoma cells. | Pharmacological research | 16 | 21145398 |
| 1988 | Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells. | Mutation research | 16 | 2896299 |
| 2023 | Beyond genetics: Deciphering the impact of missense variants in CAD deficiency. | Journal of inherited metabolic disease | 15 | 37540500 |
| 2022 | Persistent CAD activity in memory CD8+ T cells supports rRNA synthesis and ribosomal biogenesis required at rechallenge. | Science immunology | 15 | 35622902 |
| 2021 | Engineering the Cad pathway in Escherichia coli to produce glutarate from L-lysine. | Applied microbiology and biotechnology | 15 | 33907891 |
| 1987 | Transcriptional regulation of the human CAD gene during myeloid differentiation. | Molecular and cellular biology | 15 | 2885743 |
| 2020 | Exploring Metabolic Consequences of CPS1 and CAD Dysregulation in Hepatocellular Carcinoma by Network Reconstruction. | Journal of hepatocellular carcinoma | 14 | 32021853 |
| 2006 | The apoptotic endonuclease DFF40/CAD is inhibited by RNA, heparin and other polyanions. | Apoptosis : an international journal on programmed cell death | 14 | 16699957 |
| 2018 | Association of rs662799 in APOA5 with CAD in Chinese Han population. | BMC cardiovascular disorders | 13 | 29310573 |
| 2014 | carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (cad) regulates Notch signaling and vascular development in zebrafish. | Developmental dynamics : an official publication of the American Association of Anatomists | 13 | 25294789 |
| 2020 | Computer-Aided Design and Manufacturing (CAD/CAM) for Bioprinting. | Methods in molecular biology (Clifton, N.J.) | 12 | 32207104 |
| 2012 | Expression, purification, crystallization and preliminary X-ray diffraction analysis of the dihydroorotase domain of human CAD. | Acta crystallographica. Section F, Structural biology and crystallization communications | 12 | 23143245 |
| 2008 | Endosomal colocalization of melanocortin-3 receptor and beta-arrestins in CAD cells with altered modification of AKT/PKB. | Neuropeptides | 12 | 18291523 |
| 2007 | Extracellular cAMP inhibits D1 dopamine receptor expression in CAD catecholaminergic cells via A2a adenosine receptors. | Journal of neurochemistry | 12 | 17254022 |
| 2021 | CAD Genes: Genome-Wide Identification, Evolution, and Their Contribution to Lignin Biosynthesis in Pear (Pyrus bretschneideri). | Plants (Basel, Switzerland) | 11 | 34371647 |
| 2013 | Expression, purification, crystallization and preliminary X-ray diffraction analysis of the aspartate transcarbamoylase domain of human CAD. | Acta crystallographica. Section F, Structural biology and crystallization communications | 11 | 24316846 |