Pcyt1a

Summary

Gene Symbol: Pcyt1a
Description: phosphate cytidylyltransferase 1, choline, alpha isoform
Alias: CTalpha, Cctalpha, Ctpct, Cttalpha, choline-phosphate cytidylyltransferase A, CCT A, CCT-alpha, CT A, CTP phosphocholine cytidylyl transferase, CTP:phosphocholine cytidylyltransferase A, CTP:phosphocholine cytidylyltransferase alpha, phosphorylcholine transferase A
Species: mouse
Products:     Pcyt1a

Top Publications

  1. Chen B, Mallampalli R. Calmodulin binds and stabilizes the regulatory enzyme, CTP: phosphocholine cytidylyltransferase. J Biol Chem. 2007;282:33494-506 pubmed
    CTP:phosphocholine cytidylyltransferase (CCTalpha) is a proteolytically sensitive enzyme essential for production of phosphatidylcholine, the major phospholipid of animal cell membranes...
  2. 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
    ..Cytidylyltransferase (CCTalpha) is a proteolytically sensitive lipogenic enzyme containing an NH(2)-terminal nuclear localization signal (NLS)...
  3. Agassandian M, Chen B, Schuster C, Houtman J, Mallampalli R. 14-3-3zeta escorts CCTalpha for calcium-activated nuclear import in lung epithelia. FASEB J. 2010;24:1271-83 pubmed publisher
    ..Phosphatidylcholine, an indispensible membrane component, requires the enzyme CCTalpha for its biosynthesis...
  4. Wang L, Magdaleno S, Tabas I, Jackowski S. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol Cell Biol. 2005;25:3357-63 pubmed
    ..Multiple CCT isoforms, CCTalpha, CCTbeta2, and CCTbeta3, are encoded by two genes, Pcyt1a and Pcyt1b...
  5. Agassandian M, Zhou J, Tephly L, Ryan A, Carter A, Mallampalli R. Oxysterols inhibit phosphatidylcholine synthesis via ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase. J Biol Chem. 2005;280:21577-87 pubmed
    ..synthesis by increasing phosphorylation of the regulatory enzyme CTP:phosphocholine cytidylyltransferase-alpha (CCTalpha). Phosphorylation of CCTalpha decreased its activity...
  6. Jackowski S, Fagone P. CTP: Phosphocholine cytidylyltransferase: paving the way from gene to membrane. J Biol Chem. 2005;280:853-6 pubmed
  7. Ling J, Zhu L, Vance D, Jacobs R. Impaired phosphatidylcholine biosynthesis does not attenuate liver regeneration after 70% partial hepatectomy in hepatic CTP:phosphocholine cytidylyltransferase-? deficient mice. Can J Physiol Pharmacol. 2012;90:1403-12 pubmed publisher
    ..We conclude that CT? is not essential for proliferation of hepatocytes in vivo, and that basal hepatic PC biosynthesis is sufficient to sustain regeneration after 70% partial hepatectomy. ..
  8. Goulbourne C, Malhas A, Vaux D. The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-?. J Cell Sci. 2011;124:4253-66 pubmed publisher
    ..Both types of invagination can co-exist in one nucleus and both are frequently studded with nuclear pore complexes (NPC), which reduces NPC abundance on the nuclear surface. ..
  9. Jacobs R, Devlin C, Tabas I, Vance D. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins. J Biol Chem. 2004;279:47402-10 pubmed
    ..To ascertain the functional importance of CTalpha, we created a mouse in which the hepatic CTalpha gene was specifically inactivated by the Cre/LoxP procedure...

More Information

Publications45

  1. 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 major phospholipid of animal cell membranes, requires the key enzyme cytidylyltransferase (CCTalpha). Cysteine sulfhydryls within CCTalpha are needed for full catalytic activity...
  2. 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
    ..increase in the activity of the rate-regulatory surfactant enzyme, CTP:phosphocholine cytidylyltransferase (CCTalpha)...
  3. Elena C, Banchio C. Specific interaction between E2F1 and Sp1 regulates the expression of murine CTP:phosphocholine cytidylyltransferase alpha during the S phase. Biochim Biophys Acta. 2010;1801:537-46 pubmed publisher
    CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) is a key enzyme for phosphatidylcholine biosynthesis in mammalian cells...
  4. Sugimoto H, Okamura K, Sugimoto S, Satou M, Hattori T, Vance D, et al. Sp1 is a co-activator with Ets-1, and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem. 2005;280:40857-66 pubmed
    ..site located at -49/-47 in the promoter of Pcyt1a as an important transcriptional element involved in basal CTalpha transcription (Sugimoto, H., Sugimoto, S., Tatei, K., Obinata, H., Bakovic, M., Izumi, T., and Vance, D. E...
  5. 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. ..
  6. 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. ..
  7. Karim M, Jackson P, Jackowski S. Gene structure, expression and identification of a new CTP:phosphocholine cytidylyltransferase beta isoform. Biochim Biophys Acta. 2003;1633:1-12 pubmed
    ..b>CCTalpha is expressed in all tissues, and is most abundant in liver, kidney and heart...
  8. Gao L, Rabbitt E, Condon J, Renthal N, Johnston J, Mitsche M, et al. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition. J Clin Invest. 2015;125:2808-24 pubmed publisher
    ..These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process. ..
  9. Hynes G, Willison K. Individual subunits of the eukaryotic cytosolic chaperonin mediate interactions with binding sites located on subdomains of beta-actin. J Biol Chem. 2000;275:18985-94 pubmed
    ..Interactions between (35)S-beta-actin and isolated CCTalpha, CCTbeta, CCTepsilon, or CCTtheta subunits are observed, suggesting that polar and electrostatic interactions may ..
  10. Ridsdale R, Post M. Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells. Am J Physiol Lung Cell Mol Physiol. 2004;287:L743-51 pubmed
  11. Ridsdale R, Tseu I, Wang J, Post M. CTP:phosphocholine cytidylyltransferase alpha is a cytosolic protein in pulmonary epithelial cells and tissues. J Biol Chem. 2001;276:49148-55 pubmed
    ..The localization of CCT alpha in lung epithelial cells and, of greater consequence, lung tissues are yet unknown...
  12. Jacobs R, Stead L, Devlin C, Tabas I, Brosnan M, Brosnan J, et al. Physiological regulation of phospholipid methylation alters plasma homocysteine in mice. J Biol Chem. 2005;280:28299-305 pubmed
    ..methylation demand and Hcy metabolism in liver-specific CTP:phosphocholine cytidylyltransferase-alpha (CTalpha) knockout mice, since flux through the phosphatidylethanolamine N-methyltransferase pathway is increased 2-fold ..
  13. 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
    ..Herein, we present the complete structure of the murine CT (Ctpct) gene...
  14. Bakovic M, Waite K, Tang W, Tabas I, Vance D. Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene (Ctpct): combined action of upstream stimulatory and inhibitory cis-acting elements. Biochim Biophys Acta. 1999;1438:147-65 pubmed
    ..However, the proximal regulatory elements for the gene (Ctpct) that encode this enzyme and the cognate transcription factors involved have not been characterized...
  15. Agassandian M, Chen B, Pulijala R, Kaercher L, Glasser J, Mallampalli R. Calcium-calmodulin kinase I cooperatively regulates nucleocytoplasmic shuttling of CCT? by accessing a nuclear export signal. Mol Biol Cell. 2012;23:2755-69 pubmed publisher
    ..Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and assembly of a CaMKI-14-3-3 ?-CCT? complex is a key effector mechanism that drives nuclear CCT? translocation. ..
  16. 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
    ..To clarify the role of CCTalpha in lung surfactant maturation, we overexpressed CCTalpha(1-367) using the surfactant protein-C promoter...
  17. Niebergall L, Jacobs R, Chaba T, Vance D. Phosphatidylcholine protects against steatosis in mice but not non-alcoholic steatohepatitis. Biochim Biophys Acta. 2011;1811:1177-85 pubmed publisher
    ..These results show that normalizing the amount of hepatic PC is not sufficient to prevent NASH in LCT?(-/-) mice. ..
  18. 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
    ..Enforced expression of either CK(alpha) or CCTalpha increased the rate of synthesis and the amount of PtdCho, and these cells initiated differentiation without RA ..
  19. van der Veen J, Lingrell S, Vance D. The membrane lipid phosphatidylcholine is an unexpected source of triacylglycerol in the liver. J Biol Chem. 2012;287:23418-26 pubmed publisher
    ..Thus, lipoprotein-associated PC should be considered a quantitatively significant source of triacylglycerol for the etiology of hepatic steatosis. ..
  20. Kim S, Oh E, Yun M, Lee S, Chae G. Palmitate induces cisternal ER expansion via the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells. Lipids Health Dis. 2015;14:73 pubmed publisher
    ..The findings reported herein indicate that palmitate-induced cisternal ER expansion is dependent on the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells. ..
  21. Fagone P, Gunter C, Sage C, Gunn K, Brewer J, Jackowski S. CTP:phosphocholine cytidylyltransferase alpha is required for B-cell proliferation and class switch recombination. J Biol Chem. 2009;284:6847-54 pubmed publisher
    ..b>CCTalpha is the predominant isoform expressed in mammalian cells...
  22. Jacobs R, Lingrell S, Zhao Y, Francis G, Vance D. Hepatic CTP:phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein. J Biol Chem. 2008;283:2147-55 pubmed
    ..We previously generated a mouse in which the hepatic CTalpha gene was specifically inactivated by the cre/loxP procedure...
  23. Banchio C, Lingrell S, Vance D. Role of histone deacetylase in the expression of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem. 2006;281:10010-5 pubmed
    ..The molecular mechanisms involved in cell-specific expression of CTP:phosphocholine cytidylyltransferase alpha (CTalpha) are not fully understood...
  24. 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
    ..Previous studies demonstrated that the mRNA encoding CTP:phosphocholine cytidylyltransferase alpha (CTalpha) increases during S phase (Golfman, L. S., Bakovic, M., and Vance, D. E. (2001) J. Biol. Chem...
  25. 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. ..
  26. Mallampalli R, Ryan A, Carroll J, Osborne T, Thomas C. Lipid deprivation increases surfactant phosphatidylcholine synthesis via a sterol-sensitive regulatory element within the CTP:phosphocholine cytidylyltransferase promoter. Biochem J. 2002;362:81-8 pubmed
    ..These observations indicate that sterol-regulated expression of CCT is mediated by an SRE within its 5' flanking region. ..
  27. 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
    ..CTP:phosphocholine cytidylyltransferase is a major regulator of phosphatidylcholine biosynthesis. A single isoform, CCTalpha, has been studied extensively and a second isoform, CCTbeta, was recently identified...
  28. Tian Y, Zhou R, Rehg J, Jackowski S. Role of phosphocholine cytidylyltransferase alpha in lung development. Mol Cell Biol. 2007;27:975-82 pubmed
    ..Previous studies have shown a strict dependence on the choline cytidylyltransferase alpha isoform (CCTalpha) to mediate membrane phospholipid formation in cultured cells and during preimplantation embryogenesis...
  29. 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
    CTP:phosphocholine cytidylyltransferase (CCTalpha) is a rate-regulatory enzyme required for phosphatidylcholine (PtdCho) synthesis. CCTalpha is also a phosphoenzyme, but the physiologic role of kinases on enzyme function remains unclear...
  30. 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
    ..Immunoblot analyses demonstrated that twice as much CCTalpha was associated with plasma membrane in livers of Scd1-/- compared with wild type mice, suggesting that Scd1 ..
  31. Chen B, Coon T, Glasser J, Mallampalli R. Calmodulin antagonizes a calcium-activated SCF ubiquitin E3 ligase subunit, FBXL2, to regulate surfactant homeostasis. Mol Cell Biol. 2011;31:1905-20 pubmed publisher
    ..The results provide a unique model of calcium-regulated intermolecular competition between an E3 ligase subunit and an antagonist that is critically relevant to pneumonia and lipid homeostasis. ..
  32. Krahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, Heger K, et al. Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab. 2011;14:504-15 pubmed publisher
    ..Our results reveal a mechanism to maintain PC homeostasis at the expanding LD monolayer through targeted activation of a key PC synthesis enzyme. ..
  33. 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
    CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) contains a central region that functions as a catalytic domain, converting phosphocholine and cytidine 5'-triphosphate (CTP) to CDP-choline for the subsequent synthesis of ..
  34. Joza S, Wang J, Fox E, Hillman V, Ackerley C, Post M. Loss of semaphorin-neuropilin-1 signaling causes dysmorphic vascularization reminiscent of alveolar capillary dysplasia. Am J Pathol. 2012;181:2003-17 pubmed publisher
    ..These findings indicate a critical role for Sema3-Nrp1 signaling in fetal pulmonary development, which may have clinical relevance for treatment of various neonatal respiratory disorders, including alveolar capillary dysplasia. ..
  35. Zhang D, Tang W, Yao P, Yang C, Xie B, Jackowski S, et al. Macrophages deficient in CTP:Phosphocholine cytidylyltransferase-alpha are viable under normal culture conditions but are highly susceptible to free cholesterol-induced death. Molecular genetic evidence that the induction of phosphatidylcholine biosy. J Biol Chem. 2000;275:35368-76 pubmed
    ..To test this hypothesis directly, we created mice with macrophage-targeted disruption of the major CT gene, CTalpha, using the Cre-lox system...
  36. 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
    ..A genomic clone was isolated and the chromosomal location of the Ctpct locus determined by Southern blot hybridization of DNAs from a panel of interspecific backcross progeny derived ..