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Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase

Aspartate Carbamoyltransferase, Dihydroorotase, ura4
The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: ACID, CAN, HAD, STEP, V1a
Papers on Aspartate Carbamoyltransferase
Versatile function of the circadian protein CIPC as a regulator of Erk activation.
Konishi et al., Shōbara, Japan. In Biochem Biophys Res Commun, Feb 2016
We identified CIPC-binding proteins such as the multifunctional enzyme CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase), which is a key enzyme for de novo pyrimidine synthesis.
Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.
Siena et al., Milano, Italy. In Br J Cancer, Jan 2016
RESULTS: A novel ALK fusion with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) was identified.
New cassettes for single-step drug resistance and prototrophic marker switching in fission yeast.
Lorenz, Aberdeen, United Kingdom. In Yeast, Dec 2015
Moreover, strains with single gene deletions or tags often already exist in strain collections; for historical reasons these will mostly carry the ura4(+) gene or the G418-resistance kanMX as marker.
Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis.
Erez et al., Israel. In Nature, Dec 2015
Here we show that decreased activity of ASS1 in cancers supports proliferation by facilitating pyrimidine synthesis via CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) activation.
A vector system for efficient and economical switching of a ura4(+) module to three commonly used antibiotic marker cassettes in Schizosaccharomyces pombe.
Jin et al., Xiamen, China. In Yeast, Nov 2015
We describe here the development of a set of plasmid vectors that allow simple, efficient and economical switching of a ura4(+) module in existing Schizosaccharomyces pombe strains to any of the three routinely used antibiotic marker cassettes, kanMX6, hphMX6 and natMX6.
Cell Lysis in S. pombe ura4 Mutants Is Suppressed by Loss of Functional Pub1, Which Regulates the Uracil Transporter Fur4.
Kawamukai et al., Matsue, Japan. In Plos One, 2014
Schizosaccharomyces pombe Δura4 cells lyse when grown on YPD medium.
Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1.
Manning et al., Boston, United States. In Science, 2013
mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis.
Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis.
Hall et al., Basel, Switzerland. In Science, 2013
mTOR controlled the phosphorylation of 335 proteins, including CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase).
Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence.
Cabon et al., Villejuif, France. In Faseb J, 2012
findings show that in prostate tumor cells, CAD fosters androgen receptor translocation into the nucleus and stimulates its transcriptional activity; in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but a higher CAD mRNA level was associated with local tumor extension and cancer relapse
Dare to challenge the silence? Telomeric gene silencing revisited.
Yankulov, Guelph, Canada. In Nucleus, 2011
The gene silencing analyses in these species very often include the FOA-sensitivity assay, which detects the suppression of a reporter gene (URA3 in S. cerevisiae and URA4 in S. pombe) inserted at genomic locations of choice.
Leflunomide: a drug with a potential beyond rheumatology.
Burst et al., Köln, Germany. In Immunotherapy, 2010
Leflunomide, an inhibitor of the dihydroorotase dehydrogenase and thereby pyrimidine synthesis, was introduced and licensed for the treatment of rheumatoid arthritis in 1998.
Human carbamoyl-phosphate synthetase: insight into N-acetylglutamate interaction and the functional effects of a common single nucleotide polymorphism.
Powers-Lee et al., Boston, United States. In J Inherit Metab Dis, 2008
hCPS_DeltaA was not able to fully assume the catalytically competent conformation, with specific activity of CP formation decreased 700-fold.
Contribution of CDP/Cux, a transcription factor, to cell cycle progression.
Liang et al., Suzhou, China. In Acta Biochim Biophys Sin (shanghai), 2007
The generation of CDP/Cux p110 stimulates the expression of reporter plasmid containing the promoter sequences of some S phase-specific-genes such as DNA polymerase a gene, dihydrofolate reductase gene, carbamoyl-phosphate synthase/aspartate carbamoyl-transferase/dihydroorotase gene, and cyclin A gene.
Studies on the mechanism of RNAi-dependent heterochromatin assembly.
Gygi et al., Boston, United States. In Cold Spring Harb Symp Quant Biol, 2005
In support of this possibility, tethering of the RITS complex to the transcript of the normally euchromatic ura4 (+) gene results in siRNA generation and RNAi- and heterochromatin-dependent silencing of the ura4 (+) gene.
Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD.
Guy et al., Detroit, United States. In J Biol Chem, 2005
the nuclear import of CAD appears to promote optimal cell growth
Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha.
Tsai et al., Tainan City, Taiwan. In Nucleic Acids Res, 2004
cad gene expression is repressed by hypoxia-inducible factor-1alpha, which represents a functional link between hypoxia and cell-cycle arrest.
Metabolic channelling of carbamoyl phosphate in the hyperthermophilic archaeon Pyrococcus furiosus: dynamic enzyme-enzyme interactions involved in the formation of the channelling complex.
Glansdorff et al., Brussels, Belgium. In Biochem Soc Trans, 2004
The CP channelling complex involving CKase and OTCase or ATCase (aspartate carbamoyltransferase), identified in hyperthermophilic archaea, provides a good model system to investigate the mechanism of metabolic channelling and the molecular basis of protein-protein interactions in the physiology of extreme thermophiles.
mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad.
Sif et al., Columbus, United States. In Mol Cell Biol, 2003
Data show that PRMT5 can be found in association with hSWI/SNF complexes and is involved in regulating the expression of carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase.
Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis.
Klar et al., Frederick, United States. In Cell, 1996
In a strain carrying replacement of 7.5 kb of the K-region with the ura4 gene, we discovered that ura4 silencing and efficiency of mating-type switching were covariegated and were regulated by an epigenetic mechanism.
Position effect variegation at fission yeast centromeres.
Cranston et al., Edinburgh, United Kingdom. In Cell, 1994
The insertion of the ura4 gene within these centromeres resulted in genetically identical cells mosaic for its expression.
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