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Gene Review

PCT1  -  choline-phosphate cytidylyltransferase

Saccharomyces cerevisiae S288c

Synonyms: BSR2, CCT, CCT1, CT, CTP:phosphocholine cytidylyltransferase, ...
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Disease relevance of PCT1

  • E. coli MM294/pUCK3 and MM294/pCC41 cells, which express a choline kinase from Saccharomyces cerevisiae (CKIase; encoded by the CKI gene) and a cholinephosphate cytidylyltransferase from S. cerevisiae (CCTase; encoded by the CCT gene) respectively, were added to this CTP-producing reaction system [1].
  • Expression of yeast CCT in a baculovirus system as a 6x-His-tag fusion protein was higher and was used to purify yeast CCT by a procedure that included delipidation [2].
  • Based on the specificity of the Htt-CCT1 interaction, the CCT1 substrate-binding domain may provide a versatile scaffold for therapeutic inhibitors of neurodegenerative disease [3].
  • Conversely, overexpression of a single TRiC subunit, CCT1, is sufficient to remodel Htt-aggregate morphology in vivo and in vitro, and reduces Htt-induced toxicity in neuronal cells [3].
  • Furthermore, it shows less, but significant, similarity to yeast ET as well as to other cytidylyltransferases, including rat CTP:phosphocholine cytidylyltransferase and Bacillus subtilis glycerol-3-phosphate cytidylyltransferase [4].

High impact information on PCT1

  • In vivo, CCT is essential for Cdc20-dependent cell cycle events such as sister chromatid separation and exit from mitosis [5].
  • Here, we show that the hetero-oligomeric chaperonin TRiC (also known as CCT) physically interacts with polyglutamine-expanded variants of huntingtin (Htt) and effectively inhibits their aggregation [3].
  • The role in protein folding of the eukaryotic chaperonin TRiC/CCT is only partially understood [6].
  • During plant evolution, the number of genes encoding HAP proteins was greatly amplified, and these proteins may have acquired novel functions, such as mediating the effect of CCT domain proteins on gene expression [7].
  • The CCT (for CONSTANS, CONSTANS-LIKE, TOC1) domain is found in 45 Arabidopsis thaliana proteins involved in processes such as photoperiodic flowering, light signaling, and regulation of circadian rhythms [7].

Chemical compound and disease context of PCT1


Biological context of PCT1


Anatomical context of PCT1

  • The CTP: phosphocholine cytidylyltransferase (CT) gene from yeast and cDNA from rat liver were over-expressed 20-30-fold in COS cells [13].
  • Dark-grown transgenic Arabidopsis seedlings expressing the C-terminal domains (CCT) of the cryptochrome (CRY) blue light photoreceptors exhibit features that are normally associated only with light-grown seedlings, indicating that the signaling mechanism of Arabidopsis CRY is mediated through CCT [14].
  • Thus, the loss of cross-linking efficiency suggested that contact sites at the dimer interface had increased distance or reduced flexibility upon binding of CCT to membranes [15].
  • We propose that the antagonistic actions of PhLP3 and prefoldin serve to modulate CCT activity and play a key role in establishing a functional cytoskeleton in vivo [16].
  • Among the group II chaperonins, CCT proteins provide crucial machinery for the stabilization and proper folding of several proteins in the cytosol of eukaryotic cells through interactions that are subunit-specific and geometry-dependent [17].

Associations of PCT1 with chemical compounds

  • Metabolic studies determined that phosphatidylcholine biosynthesis decreased to negligible levels within 1 h upon shift to the nonpermissive temperature for the temperature-sensitive PCT1 allele [10].
  • We now report that SEC14p effects an in vivo depression of CDP-choline pathway activity by inhibiting choline-phosphate cytidylyltransferase (CCTase; EC, the rate-determining enzyme of the CDP-choline pathway [18].
  • The concentration optima for the activation of Y-CT by oleic acid or anionic phospholipids were 5-10-fold lower than those for R-CT [13].
  • Y-CT activity was insensitive to PC vesicles containing the neutral lipids diacylglycerol, monoacylglycerol or oleyl alcohol [13].
  • The positively charged aminolipid sphingosine antagonized the stimulation by oleic acid of both Y-CT and R-CT [13].

Other interactions of PCT1

  • This CCT/CKI fused protein retained both activities and the thermal stability of its cholinephosphate cytidylyltransferase activity was nearly the same as the native CCT enzyme [19].
  • Three genes had already been cloned and sequenced: CCT, ADE3 and TR-I [20].

Analytical, diagnostic and therapeutic context of PCT1


  1. Enzymatic production of pyrimidine nucleotides using Corynebacterium ammoniagenes cells and recombinant Escherichia coli cells: enzymatic production of CDP-choline from orotic acid and choline chloride (Part I). Fujio, T., Maruyama, A. Biosci. Biotechnol. Biochem. (1997) [Pubmed]
  2. Purification and kinetic characterization of CTP:phosphocholine cytidylyltransferase from Saccharomyces cerevisiae. Friesen, J.A., Park, Y.S., Kent, C. Protein Expr. Purif. (2001) [Pubmed]
  3. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Tam, S., Geller, R., Spiess, C., Frydman, J. Nat. Cell Biol. (2006) [Pubmed]
  4. Cloning and expression of CTP:phosphoethanolamine cytidylyltransferase cDNA from rat liver. Bladergroen, B.A., Houweling, M., Geelen, M.J., van Golde, L.M. Biochem. J. (1999) [Pubmed]
  5. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Camasses, A., Bogdanova, A., Shevchenko, A., Zachariae, W. Mol. Cell (2003) [Pubmed]
  6. TRiC/CCT cooperates with different upstream chaperones in the folding of distinct protein classes. Siegers, K., Bölter, B., Schwarz, J.P., Böttcher, U.M., Guha, S., Hartl, F.U. EMBO J. (2003) [Pubmed]
  7. CONSTANS and the CCAAT Box Binding Complex Share a Functionally Important Domain and Interact to Regulate Flowering of Arabidopsis. Wenkel, S., Turck, F., Singer, K., Gissot, L., Le Gourrierec, J., Samach, A., Coupland, G. Plant Cell (2006) [Pubmed]
  8. Molecular cloning of CTP:phosphocholine cytidylyltransferase from Plasmodium falciparum. Yeo, H.J., Sri Widada, J., Mercereau-Puijalon, O., Vial, H.J. Eur. J. Biochem. (1995) [Pubmed]
  9. Investigation of a choline phosphate synthesis pathway in Streptococcus pneumoniae: evidence for choline phosphate cytidylyltransferase activity. Whiting, G.C., Gillespie, S.H. FEMS Microbiol. Lett. (1996) [Pubmed]
  10. Cessation of growth to prevent cell death due to inhibition of phosphatidylcholine synthesis is impaired at 37 degrees C in Saccharomyces cerevisiae. Howe, A.G., Zaremberg, V., McMaster, C.R. J. Biol. Chem. (2002) [Pubmed]
  11. Expression in Escherichia coli of the Saccharomyces cerevisiae CCT gene encoding cholinephosphate cytidylyltransferase. Tsukagoshi, Y., Nikawa, J., Hosaka, K., Yamashita, S. J. Bacteriol. (1991) [Pubmed]
  12. Molecular cloning and characterization of the gene encoding cholinephosphate cytidylyltransferase in Saccharomyces cerevisiae. Tsukagoshi, Y., Nikawa, J., Yamashita, S. Eur. J. Biochem. (1987) [Pubmed]
  13. Comparison of the lipid regulation of yeast and rat CTP: phosphocholine cytidylyltransferase expressed in COS cells. Johnson, J.E., Kalmar, G.B., Sohal, P.S., Walkey, C.J., Yamashita, S., Cornell, R.B. Biochem. J. (1992) [Pubmed]
  14. The signaling mechanism of Arabidopsis CRY1 involves direct interaction with COP1. Yang, H.Q., Tang, R.H., Cashmore, A.R. Plant Cell (2001) [Pubmed]
  15. Membrane binding modulates the quaternary structure of CTP:phosphocholine cytidylyltransferase. Xie, M., Smith, J.L., Ding, Z., Zhang, D., Cornell, R.B. J. Biol. Chem. (2004) [Pubmed]
  16. PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates. Stirling, P.C., Cuéllar, J., Alfaro, G.A., El Khadali, F., Beh, C.T., Valpuesta, J.M., Melki, R., Leroux, M.R. J. Biol. Chem. (2006) [Pubmed]
  17. Positive selection and subfunctionalization of duplicated CCT chaperonin subunits. Fares, M.A., Wolfe, K.H. Mol. Biol. Evol. (2003) [Pubmed]
  18. The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity. Skinner, H.B., McGee, T.P., McMaster, C.R., Fry, M.R., Bell, R.M., Bankaitis, V.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  19. Construction of a plasmid carrying both CTP synthetase and a fused gene formed from cholinephosphate cytidylyltransferase and choline kinase genes and its application to industrial CDP-choline production: enzymatic production of CDP-choline from orotic acid (Part II). Fujio, T., Teshiba, S., Maruyama, A. Biosci. Biotechnol. Biochem. (1997) [Pubmed]
  20. Sequencing of a 17.6 kb segment on the right arm of yeast chromosome VII reveals 12 ORFs, including CCT, ADE3 and TR-I genes, homologues of the yeast PMT and EF1G genes, of the human and bacterial electron-transferring flavoproteins (beta-chain) and of the Escherichia coli phosphoserine phosphohydrolase, and five new ORFs. Guerreiro, P., Barreiros, T., Soares, H., Cyrne, L., Maia e Silva, A., Rodrigues-Pousada, C. Yeast (1996) [Pubmed]
  21. Three-dimensional analysis of protein aggregate body in Saccharomyces cerevisiae cells. Kamasawa, N., Yoshida, T., Ueda, M., Tanaka, A., Osumi, M. Journal of electron microscopy. (1999) [Pubmed]
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