choline phosphate cytidylyltransferase


Summary: An enzyme that catalyzes the transfer of cytidylate (CMP) to choline phosphate to form CDPcholine. It is the rate-limiting enzyme in the choline pathway for the biosynthesis of phosphatidylcholine. Its activity is increased by glucocorticoids. EC

Top Publications

  1. Ridsdale R, Tseu I, Roth Kleiner M, Wang J, Post M. Increased phosphatidylcholine production but disrupted glycogen metabolism in fetal type II cells of mice that overexpress CTP:phosphocholine cytidylyltransferase. J Biol Chem. 2004;279:55946-57 pubmed
    ..We conclude that overexpression of CCTalpha increases surfactant PtdCho synthesis without affecting surfactant protein levels but that it disrupts glycogen metabolism in differentiating type II cells via its regulatory domain. ..
  2. Tilley D, Evans C, Larson T, Edwards K, Friesen J. Identification and characterization of the nuclear isoform of Drosophila melanogaster CTP:phosphocholine cytidylyltransferase. Biochemistry. 2008;47:11838-46 pubmed publisher
    ..The cellular location of both CCT1 and CCT2 isoforms was elucidated by expressing green fluorescent fusion proteins in cultured D. melanogaster Schneider 2 cells. CCT1 was identified as the nuclear isoform, while CCT2 is cytoplasmic. ..
  3. Gupta T, Schupbach T. Cct1, a phosphatidylcholine biosynthesis enzyme, is required for Drosophila oogenesis and ovarian morphogenesis. Development. 2003;130:6075-87 pubmed
    ..These data provide the first evidence for a specific role for CCT, and thus for phosphatidylcholine, in patterning during development. ..
  4. Cornell R, Northwood I. Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization. Trends Biochem Sci. 2000;25:441-7 pubmed
    ..Recently, a new level of its regulation has emerged with the discovery that signals that stimulate PC synthesis recruit CCT alpha from an inactive nuclear reservoir to a functional site on the endoplasmic reticulum. ..
  5. Lykidis A, Murti K, Jackowski S. Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. J Biol Chem. 1998;273:14022-9 pubmed
    ..These data demonstrate that a second, distinct CCT enzyme is expressed in human tissues and provides another mechanism by which cells regulate phosphatidylcholine production. ..
  6. Helmink B, Friesen J. Characterization of a lipid activated CTP:phosphocholine cytidylyltransferase from Drosophila melanogaster. Biochim Biophys Acta. 2004;1683:78-88 pubmed
  7. Ramos B, El Mouedden M, Claro E, Jackowski S. Inhibition of CTP:phosphocholine cytidylyltransferase by C(2)-ceramide and its relationship to apoptosis. Mol Pharmacol. 2002;62:1068-75 pubmed
    ..Taken together, our results suggest CCT as a primary target for C(2)-ceramide inhibition that accounts for its cytotoxic effects. ..
  8. Lykidis A, Baburina I, Jackowski S. Distribution of CTP:phosphocholine cytidylyltransferase (CCT) isoforms. Identification of a new CCTbeta splice variant. J Biol Chem. 1999;274:26992-7001 pubmed
  9. Davies S, Epand R, Kraayenhof R, Cornell R. Regulation of CTP: phosphocholine cytidylyltransferase activity by the physical properties of lipid membranes: an important role for stored curvature strain energy. Biochemistry. 2001;40:10522-31 pubmed
    ..Cholesterol, a poor activator of CT, did not affect the positioning of the polarity-sensitive probe, suggesting that one reason for its ineffectiveness is an inability to enhance surface hydrophobicity. ..

More Information


  1. Fernández Tome M, Speziale E, Sterin Speziale N. Phospholipase C inhibitors and prostaglandins differentially regulate phosphatidylcholine synthesis in rat renal papilla. Evidence of compartmental regulation of CTP:phosphocholine cytidylyltransferase and CDP-choline:1,2-diacylglycerol cholinephosph. Biochim Biophys Acta. 2002;1583:185-94 pubmed
    ..Such regulation might occur at least at two different levels of the CDP-choline pathway: on the one hand, PLC operates on CCT activity; on the other, while PGs regulate CPT activity. ..
  2. van der Sanden M, Houweling M, van Golde L, Vaandrager A. Inhibition of phosphatidylcholine synthesis induces expression of the endoplasmic reticulum stress and apoptosis-related protein CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Biochem J. 2003;369:643-50 pubmed
    ..These results suggest that PC depletion in MT58 induces the ER-stress-related protein CHOP, without raising a general ER stress response. ..
  3. Jackowski S, Wang J, Baburina I. Activity of the phosphatidylcholine biosynthetic pathway modulates the distribution of fatty acids into glycerolipids in proliferating cells. Biochim Biophys Acta. 2000;1483:301-15 pubmed
    ..Thus, the cellular DG supply did not regulate PtdCho biosynthesis and CCT activity governs the partitioning of DG into either the PL or TG pools, thereby controlling both PtdCho and TG biosynthesis...
  4. Gunter C, Frank M, Tian Y, Murti K, Rehg J, Jackowski S. Probucol therapy overcomes the reproductive defect in CTP: phosphocholine cytidylyltransferase beta2 knockout mice. Biochim Biophys Acta. 2007;1771:845-52 pubmed
    ..These data indicated that a deficiency in de novo PtdCho synthesis could be complemented by altering the metabolism of serum lipoproteins, an alternative source for cellular phospholipid. ..
  5. Dunne S, Cornell R, Johnson J, Glover N, Tracey A. Structure of the membrane binding domain of CTP:phosphocholine cytidylyltransferase. Biochemistry. 1996;35:11975-84 pubmed
    ..The disposition of these side chains gives clues to the basis for the specificities of these peptides for anionic surfaces. ..
  6. Ridgway N, Lagace T. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms. Biochem J. 2003;372:811-9 pubmed
    ..These data show that transcriptional activation of CCTalpha is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis. ..
  7. Li L, She H, Yue S, Qin X, Guan C, Liu H, et al. Role of c-fos gene in vasoactive intestinal peptide promoted synthesis of pulmonary surfactant phospholipids. Regul Pept. 2007;140:117-24 pubmed
    ..These results demonstrated that VIP receptors, PKC and c-Fos protein played important roles in the signaling pathway through which VIP promoted the synthesis of PC. ..
  8. Ryan A, Andrews M, Zhou J, Mallampalli R. c-Jun N-terminal kinase regulates CTP:phosphocholine cytidylyltransferase. Arch Biochem Biophys. 2006;447:23-33 pubmed
    ..These observations suggest a role for JNK kinases as negative regulators of phospholipid synthesis in murine lung epithelia. ..
  9. Ryan A, Chen B, Vennalaganti P, Henderson F, Tephly L, Carter A, et al. 15-deoxy-Delta12,14-prostaglandin J2 impairs phosphatidylcholine synthesis and induces nuclear accumulation of thiol-modified cytidylyltransferase. J Biol Chem. 2008;283:24628-40 pubmed publisher
    ..The data indicate that bioactive prostanoids significantly impair membrane phospholipid production by promoting cysteine cross-bridging within CCTalpha. ..
  10. Garbay B, Cassagne C. Expression of the ceramide galactosyltransferase gene during myelination of the mouse nervous system. Comparison with the genes encoding myelin basic proteins, choline kinase and CTP:phosphocholine cytidylyltransferase. Brain Res Dev Brain Res. 1994;83:119-24 pubmed
    ..Our results clearly indicate that the deficit in the accumulation of the galactosylceramides documented for this mutant is well correlated to a reduced CGT gene expression. ..
  11. Sugimoto H, Bakovic M, Yamashita S, Vance D. Identification of transcriptional enhancer factor-4 as a transcriptional modulator of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem. 2001;276:12338-44 pubmed
    ..These results provide the first evidence that TEF-4 is an important regulator of CCTalpha gene expression. ..
  12. Kalmar G, Kay R, LaChance A, Cornell R. Primary structure and expression of a human CTP:phosphocholine cytidylyltransferase. Biochim Biophys Acta. 1994;1219:328-34 pubmed
    ..The activity of HCT was lipid dependent. The soluble form was activated 3 to 4-fold by anionic phospholipids and by oleic acid or diacylglycerol-containing PC vesicles. ..
  13. Testerink N, van der Sanden M, Houweling M, Helms J, Vaandrager A. Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex. J Lipid Res. 2009;50:2182-92 pubmed publisher
    ..Surprisingly, protein transport at the level of the Golgi complex is impaired. Our data suggest that the transport processes at the Golgi complex are regulated by distal changes in lipid metabolism. ..
  14. Sarri E, Garcia Dorado D, Abellan A, Soler Soler J. Effects of hypoxia, glucose deprivation and acidosis on phosphatidylcholine synthesis in HL-1 cardiomyocytes. CTP:phosphocholine cytidylyltransferase activity correlates with sarcolemmal disruption. Biochem J. 2006;394:325-34 pubmed
    ..Altogether our results suggest a significant role for CCT activity in sarcolemmal disruption during ischaemia. ..
  15. Fagone P, Sriburi R, Ward Chapman C, Frank M, Wang J, Gunter C, et al. Phospholipid biosynthesis program underlying membrane expansion during B-lymphocyte differentiation. J Biol Chem. 2007;282:7591-605 pubmed
    ..This work defines a genetic and biochemical program for membrane phospholipid biogenesis that correlates with an increase in the phospholipid components of the endoplasmic reticulum and Golgi compartments in LPS-stimulated B-cells. ..
  16. Fernández Tome M, Kraemer L, Federman S, Favale N, Speziale E, Sterin Speziale N. COX-2-mediated PGD2 synthesis regulates phosphatidylcholine biosynthesis in rat renal papillary tissue. Biochem Pharmacol. 2004;67:245-54 pubmed
  17. Guan C, Zhou F, Luo Z. [Effects of vasoactive intestinal peptide on the enzyme activity of CTP: phosphorylcholine cytidylyltransferase from the rat lung]. Hunan Yi Ke Da Xue Xue Bao. 2002;27:99-101 pubmed
    ..VIP in the lung may be one of the key regulators involved in the synthesis of phosphatidylcholine mediated by PKC and calmodulin. ..
  18. Rutherford M, Rock C, Jenkins N, Gilbert D, Tessner T, Copeland N, et al. The gene for murine CTP:phosphocholine cytidylyltransferase (Ctpct) is located on mouse chromosome 16. Genomics. 1993;18:698-701 pubmed
    ..These data place the Ctpct gene on mouse chromosome 16 between the Smst and Stf-1 genes. ..
  19. Marcucci H, Elena C, Gilardoni P, Banchio C. Characterization of the murine CTP:phosphocholine cytidylyltransferase beta gene promoter. Biochim Biophys Acta. 2008;1781:254-62 pubmed publisher
    ..However, CCTbeta3 was not detected in this cell line suggesting a different role or regulation. The activities of alternative promoters provide for greater flexibility in the control of CCTbeta isoform expression. ..
  20. Marengo B, Bottini C, La Porta C, Domenicotti C, Tessitore L. Inactivation of PEMT2 in hepatocytes initiated by DENA in fasted/refed rats. Biochem Biophys Res Commun. 2006;346:234-41 pubmed
    ..The treatment with 20 mg/kg DENA to refed rats induced the appearance of initiated hepatocytes that were negative for PEMT expression. Present findings indicate that PEMT is a novel tumour marker for early liver preneoplastic lesions. ..
  21. Jackowski S, Rehg J, Zhang Y, Wang J, Miller K, Jackson P, et al. Disruption of CCTbeta2 expression leads to gonadal dysfunction. Mol Cell Biol. 2004;24:4720-33 pubmed
    ..The results indicate that although CCTbeta2 is expressed at very low levels compared to the alpha-isoform, loss of CCTbeta2 expression causes a breakdown in the gonadal response to hormonal stimulation. ..
  22. Sriburi R, Bommiasamy H, Buldak G, Robbins G, Frank M, Jackowski S, et al. Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis. J Biol Chem. 2007;282:7024-34 pubmed
    ..We propose that XBP-1(S) regulates ER abundance by coordinately increasing the supply of membrane phospholipids and ER proteins, the key ingredients for ER biogenesis. ..
  23. Moon E, O NEILL C. CTP:phosphocholine cytidylyltransferase activity in the preimplantation mouse embryo. J Reprod Fertil. 1997;110:213-8 pubmed
    ..This study provides the first description of cytidylyltransferase in the early mammalian embryo. ..
  24. Enaw J, Zhu H, Yang W, Lu W, Shaw G, Lammer E, et al. CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population. BMC Med. 2006;4:36 pubmed
    ..Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved. ..
  25. Chen B, Mallampalli R. Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase. Mol Cell Biol. 2009;29:3062-75 pubmed publisher
    ..These results unravel a unique molecular mechanism whereby monoubiquitination governs the trafficking and life span of a critical regulatory enzyme in vivo. ..
  26. Dobrzyn A, Dobrzyn P, Miyazaki M, Sampath H, Chu K, Ntambi J. Stearoyl-CoA desaturase 1 deficiency increases CTP:choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver. J Biol Chem. 2005;280:23356-62 pubmed
    ..Our study revealed that SCD1 deficiency specifically increases CCT activity by promoting its translocation into membrane and enhances PC biosynthesis in liver. ..
  27. McCoy D, Fisher K, Robichaud J, Ryan A, Mallampalli R. Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice. Am J Respir Cell Mol Biol. 2006;35:394-402 pubmed
    ..The studies demonstrate that developmental induction of surfactant phospholipid is due, at least in part, to transcriptional activation of the CCTalpha gene. ..
  28. Dymond M, Attard G, Postle A. Testing the hypothesis that amphiphilic antineoplastic lipid analogues act through reduction of membrane curvature elastic stress. J R Soc Interface. 2008;5:1371-86 pubmed publisher
    ..Overall we find the literature data and our experimental data provide excellent support for the hypothesis, which predicts that the most potent ALP analogues will be type I lipids. ..
  29. Banchio C, Schang L, Vance D. Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. J Biol Chem. 2004;279:40220-6 pubmed
    ..These results enhance our understanding of the regulatory mechanisms involved in the expression of CTalpha in preparation for cell division. ..
  30. Landis G, Bhole D, Tower J. A search for doxycycline-dependent mutations that increase Drosophila melanogaster life span identifies the VhaSFD, Sugar baby, filamin, fwd and Cctl genes. Genome Biol. 2003;4:R8 pubmed
    ..Screening for conditional mutations that increase Drosophila life span has identified genes implicated in membrane transport, phospholipid metabolism and signaling, and actin cytoskeleton organization. ..
  31. Lykidis A, Jackson P, Jackowski S. Lipid activation of CTP: phosphocholine cytidylyltransferase alpha: characterization and identification of a second activation domain. Biochemistry. 2001;40:494-503 pubmed
    ..The data also demonstrate for the first time that the 57-residue carboxy-terminal domain in CCTalpha participates in lipid-mediated regulation and is sufficient for maximum activation of enzyme activity. ..
  32. Ryan A, Medh J, McCoy D, Salome R, Mallampalli R. Maternal loading with very low-density lipoproteins stimulates fetal surfactant synthesis. Am J Physiol Lung Cell Mol Physiol. 2002;283:L310-8 pubmed
    ..Thus the nutritional or genetic modulation of serum VLDL-triglycerides provides specific fatty acids that stimulate PtdCho synthesis and CCT activity thereby increasing surfactant content. ..
  33. Lagace T, Miller J, Ridgway N. Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase alpha during farnesol-induced apoptosis. Mol Cell Biol. 2002;22:4851-62 pubmed
    ..Activation and nuclear export of CCT alpha were early events in FOH-induced apoptosis that contributed to altered PtdCho synthesis and, in conjunction with caspase cleavage, excluded CCT alpha from the nucleus. ..
  34. Zeng X, Ma Y, Hao X. [Identification of LicC activity in pneumococcal infection]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26:337-9, 343 pubmed
    ..pneumococcal infection, especially drug resistant strain. ..
  35. Braker J, Hodel K, Mullins D, Friesen J. Identification of hydrophobic amino acids required for lipid activation of C. elegans CTP:phosphocholine cytidylyltransferase. Arch Biochem Biophys. 2009;492:10-6 pubmed publisher
    ..These results support a concerted mechanism of lipid activation that requires multiple residues on the hydrophobic face of the putative amphipathic alpha helix. ..
  36. Zhou J, You Y, Zabner J, Ryan A, Mallampalli R. The CCT promoter directs high-level transgene expression in distal lung epithelial cell lines. Am J Respir Cell Mol Biol. 2004;30:61-8 pubmed
    ..Collectively, these observations suggest that the CCT alpha construct might be useful to drive high-level, regulatable expression of heterologous proteins in alveolar epithelia. ..
  37. Taneva S, Dennis M, Ding Z, Smith J, Cornell R. Contribution of each membrane binding domain of the CTP:phosphocholine cytidylyltransferase-alpha dimer to its activation, membrane binding, and membrane cross-bridging. J Biol Chem. 2008;283:28137-48 pubmed publisher
    ..Membrane binding of a single M domain is sufficient to fully activate the enzymatic activity of the CCT dimer while sustaining the low affinity, reversible membrane interaction required for regulation of CCT activity. ..
  38. Kent C. Regulatory enzymes of phosphatidylcholine biosynthesis: a personal perspective. Biochim Biophys Acta. 2005;1733:53-66 pubmed
  39. Mages F, Macovschi O, Prigent A, Fonlupt P. Increased methylation of chloroform extractable products and CTP: cholinephosphate cytidylyltransferase in brain membrane preparations from triethyltin-intoxicated rats. Pharmacol Toxicol. 1989;65:302-5 pubmed
    ..This increase might be a compensatory mechanism for counteracting the membrane damages induced by triethyltin. ..
  40. Golfman L, Bakovic M, Vance D. Transcription of the CTP:phosphocholine cytidylyltransferase alpha gene is enhanced during the S phase of the cell cycle. J Biol Chem. 2001;276:43688-92 pubmed
    ..Instead increased transcription of the CTalpha gene occurred during the S phase of the cell cycle in preparation for mitosis. ..
  41. Attard G, Templer R, Smith W, Hunt A, Jackowski S. Modulation of CTP:phosphocholine cytidylyltransferase by membrane curvature elastic stress. Proc Natl Acad Sci U S A. 2000;97:9032-6 pubmed
    ..Our results show how a purely physical feedback signal could play a key role in the control of membrane lipid synthesis. ..
  42. Kaplan O, Cohen J. Lymphocyte activation-31P magnetic resonance studies of energy metabolism and phospholipid pathways. Immunomethods. 1994;4:139-47 pubmed
    ..Perfusion studies with high concentrations of choline and the use of dapsone, an inhibitor of phosphocholine cytidyltransferase, indicate that choline kinase plays a key role in regulating PC synthesis in human lymphocytes. ..
  43. Banchio C, Schang L, Vance D. Activation of CTP:phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Sp1. J Biol Chem. 2003;278:32457-64 pubmed
    ..This is the first elucidation of a mechanism by which expression of a key enzyme in phospholipid biosynthesis is regulated during the cell cycle. ..
  44. Helmink B, Braker J, Kent C, Friesen J. Identification of lysine 122 and arginine 196 as important functional residues of rat CTP:phosphocholine cytidylyltransferase alpha. Biochemistry. 2003;42:5043-51 pubmed
  45. Awasthi S, Vivekananda J, Awasthi V, Smith D, King R. CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-alpha, p38 MAPK, cPLA2, and 5-lipoxygenase. Am J Physiol Lung Cell Mol Physiol. 2001;281:L108-18 pubmed
    ..The other product of the activation of cPLA2, arachidonic acid, is a substrate for the synthesis of leukotrienes, which raise intracellular Ca2+ levels and complete the activation of cPLA2. ..
  46. Okamura K, Yamashita S, Ando H, Horibata Y, Aoyama C, Takagishi K, et al. Identification of nuclear localization and nuclear export signals in Ets2, and the transcriptional regulation of Ets2 and CTP:phosphocholine cytidylyltransferase alpha in tetradecanoyl-13-acetate or macrophage-colony stimulating factor stimulated RAW. Biochim Biophys Acta. 2009;1791:173-82 pubmed publisher
    ..These results suggest that the induction of Ets2 is important for CTalpha transcription by TPA and macrophage-colony stimulating factor. ..
  47. Tang W, Keesler G, Tabas I. The structure of the gene for murine CTP:phosphocholine cytidylyltransferase, Ctpct. Relationship of exon structure to functional domains and identification of transcriptional start sites and potential upstream regulatory elements. J Biol Chem. 1997;272:13146-51 pubmed
    ..These data will provide the basis for future studies on the cis- and trans-acting factors involved in Ctpct gene transcription and for the creation of induced mutant mouse models of altered CT activity. ..
  48. Slomiany A, Grabska M, Piotrowski E, Sengupta S, Morita M, Kasinathan C, et al. Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis: ethanol-induced changes in membrane biogenesis. Arch Biochem Biophys. 1994;310:247-55 pubmed
  49. Marcucci H, Paoletti L, Jackowski S, Banchio C. Phosphatidylcholine biosynthesis during neuronal differentiation and its role in cell fate determination. J Biol Chem. 2010;285:25382-93 pubmed publisher
    ..These results indicate that elevated PtdCho synthesis could mimic the RA signals and thus determine neuronal cell fate. Moreover, they could explain the key role that PtdCho plays during neuronal regeneration. ..
  50. Adibhatla R, Hatcher J, Dempsey R. Cytidine-5'-diphosphocholine affects CTP-phosphocholine cytidylyltransferase and lyso-phosphatidylcholine after transient brain ischemia. J Neurosci Res. 2004;76:390-6 pubmed
    ..01 compared to saline). These data indicate that PtdCho synthesis is impaired after brain ischemia, and CDP-choline may increase PtdCho levels by attenuating the loss of CCT activity and lyso-PtdCho formation...
  51. Kent C, Gee P, Lee S, Bian X, Fenno J. A CDP-choline pathway for phosphatidylcholine biosynthesis in Treponema denticola. Mol Microbiol. 2004;51:471-81 pubmed
    ..Thus it appears that T. denticola does contain a licCA-dependent CDP-choline pathway for phosphatidylcholine biosynthesis. ..
  52. Kwak B, Zhang Y, Yun M, Heath R, Rock C, Jackowski S, et al. Structure and mechanism of CTP:phosphocholine cytidylyltransferase (LicC) from Streptococcus pneumoniae. J Biol Chem. 2002;277:4343-50 pubmed
    ..These results provide a structural basis for assigning a specific role for magnesium in the catalytic mechanism of pneumococcal LicC. ..
  53. Ma Z, Bohrer A, Wohltmann M, Ramanadham S, Hsu F, Turk J. Studies of phospholipid metabolism, proliferation, and secretion of stably transfected insulinoma cells that overexpress group VIA phospholipase A2. Lipids. 2001;36:689-700 pubmed
    ..These findings suggest that iPLA2beta plays a signaling role in beta-cells that differs from housekeeping functions in PC biosynthesis and degradation in P388D1 and CHO cells. ..