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Gene Review

PCYT1B  -  phosphate cytidylyltransferase 1, choline,...

Homo sapiens

Synonyms: CCT B, CCT-beta, CCTB, CT B, CTB, ...
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Disease relevance of PCYT1B

  • This drop in toxicity is consistent with an observed 100-fold loss in binding capacity of the CT B subunit and a 20- to 50-fold reduction in adenylate cyclase activation by the CT A subunit [1].
  • Vibrio cholerae non-O1 strains were screened for the presence of cholera enterotoxin (CT) genes by means of digoxigenin-labelled polynucleotide CTA and CTB probes [2].
  • These results suggest that protection against autoimmune diabetes can be achieved by feeding minute amounts of a pancreas islet cell autoantigen linked to CTB and appears to involve the selective migration and retention of protective T cells into lymphoid tissues draining the site of organ injury [3].
  • We have previously shown that feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hypersensitivity reactions in systemically immune animals [4].
  • We now report that feeding small amounts of myelin basic protein (MBP) conjugated to CTB either before or after disease induction protected rats from experimental autoimmune encephalomyelitis [4].

High impact information on PCYT1B

  • Coupling of antigen-containing particles to the pentameric binding subunit of cholera toxin (CTB) has been proposed as a means for increasing antigen uptake because the CTB receptor, ganglioside GM1, is a glycolipid present in apical membranes of all intestinal epithelial cells [5].
  • To test the accessibility of enterocyte and M cell membrane glycolipids to ligands in the size ranges of viruses, bacteria, and particulate mucosal vaccines, we analyzed binding of CTB probes of different sizes to rabbit Peyer's patch epithelium [5].
  • Thus, the barrier function of the intestinal epithelial cell glycocalyx may be important in limiting microbial adherence to membrane glycolipids, and in CTB-mediated targeting of vaccines to M cells and the mucosal immune system [5].
  • CTB-coated, fluorescent microparticles (final diameter, 1.13 microns) failed to adhere to enterocytes or M cells in vivo or to well-differentiated Caco-2 intestinal epithelial cells in vitro [5].
  • Stimulation of TCR signalling in Jurkat cells resulted in localized increases in fluorescence of GPI-linked fluorescent proteins and cholera toxin B-subunit (CTB) [6].

Chemical compound and disease context of PCYT1B

  • Amino acid substitutions that caused decreased binding of mutant CT-B to ganglioside GM1 and abolished toxicity included negatively charged or large hydrophobic residues for Gly-33 and negatively or positively charged residues for Trp-88 [7].
  • The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins [8].
  • Substitution of lysine or arginine for Gly-33 did not affect immunoreactivity or GM1-binding activity of CT-B but abolished or reduced toxicity of the mutant holotoxins, respectively [7].
  • The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB) [9].
  • We now report the structure determination and 2.3-A refinement of the CTB mutant Gly 33-->Arg complexed with the GM1 oligosaccharide, as well as the 2.2-A refinement of a Gly 33-->Asp mutant of the closely related Escherichia coli heat-labile enterotoxin B-pentamer (LTB) [10].

Biological context of PCYT1B


Anatomical context of PCYT1B

  • CCTbeta protein was posttranslationally modified in COS-7 cells, resulting in slower migration during polyacrylamide gel electrophoresis [12].
  • CCTbeta transcripts were detected in human adult and fetal tissues, and very high transcript levels were found in placenta and testis [12].
  • CT-B binds to ganglioside GM1, which functions as the plasma membrane receptor for CT, and the enzymatic activity of A1 causes the toxic effects of CT on target cells [13].
  • CTB coupled to 14 nm colloidal gold (final diameter, 28.8 nm) failed to adhere to enterocytes but did adhere to M cells [5].
  • Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes [14].

Associations of PCYT1B with chemical compounds

  • Cross-linking of either CD3 or CT-B strongly induced tyrosine phosphorylation and recruitment of a ZAP-70(SH2)(2)-green fluorescent protein (GFP) fusion protein to the lipid patches [15].
  • Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin [14].
  • Moreover, FGF2 competes with FITC-CTB for the binding to cell membrane GM1 in different CHO cell lines independently of their capacity to express heparan sulfate proteoglycans [16].
  • CTB accumulation in NPC1(-) cells was abolished by expression of wild-type NPC1 but not by mutant proteins with a mutation either in the NPC domain or the sterol-sensing domain [17].
  • While both CTB and LTB bind to the GM1 ganglioside, LTB also binds to N-acetyllactosamine-terminated glycoconjugates [18].

Physical interactions of PCYT1B

  • CT consists of one A polypeptide and five B polypeptides associated by noncovalent bonds, and CT-B interacts with CT-A primarily via the A2 domain [13].

Other interactions of PCYT1B

  • Both CT B subunits and to a lesser extent CT A subunits were delivered intact to the serosal surface of the basolateral membrane [19].
  • These data indicate that GM1/ligand interaction does not necessarily lead to neuritogenesis and suggest that a specialisation of CTB, not shared by anti-GM1 antibodies or rETxB, is required to activate TrkA [20].
  • The levels of CCTbeta were highly correlated (r = 0.606) with those of the proliferating cell nuclear antigen (PCNA), which was used as an indicator of cell growth [21].
  • Expression levels of CCTbeta in tumor tissues was significantly higher than in nontumor tissues in all patients with hepatocellular carcinoma (n = 15) and 83% of patients with colonic carcinoma (n = 17) [21].
  • Moreover, the amino acid sequences of the N. coriiceps CCT beta and theta chains contained residue substitutions in the equatorial, apical, and intermediate domains that would be expected to increase the flexibility of the subunits, thus facilitating function of the chaperonin in an energy poor environment [22].

Analytical, diagnostic and therapeutic context of PCYT1B

  • We have recently shown that oral administration of microgram amounts of antigen coupled to cholera toxin B subunit (CTB), can effectively suppress systemic T cell reactivity in naive as well as in immune animals [3].
  • Higher interleukin (IL)-4 amounts were observed in both splenocytes and pancreatic lymph node (PLN) cell cultures from CTB-insulin-fed mice as soon as 4 h after the feeding [23].
  • Oligonucleotide-directed mutagenesis of ctxB was used to produce mutants of cholera toxin B subunit (CT-B) altered at residues Cys-9, Gly-33, Lys-34, Arg-35, Cys-86 and Trp-88 [7].
  • In ultrastructural studies using the scanning electron microscope (SEM) and immunofluorescence (IF) analyses to discriminate microtubule distributions, neurites of GM1-supplemented cells on CTB were virtually identical with pFN-adherent neurites, whereas unsupplemented cells on CTB generated processes with fine-structural differences [24].
  • Both oral and nasal vaccination resulted in 5- to 6-fold CTB-specific IgA and 20- to 30-fold specific IgG increases in vaginal secretions [25].


  1. Cholera toxin as a mucosal adjuvant. Glutaraldehyde treatment dissociates adjuvanticity from toxicity. Liang, X.P., Lamm, M.E., Nedrud, J.G. J. Immunol. (1989) [Pubmed]
  2. The use of gene probes, immunoassays and tissue culture for the detection of toxin in Vibrio cholerae non-O1. Said, B., Scotland, S.M., Rowe, B. J. Med. Microbiol. (1994) [Pubmed]
  3. A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes. Bergerot, I., Ploix, C., Petersen, J., Moulin, V., Rask, C., Fabien, N., Lindblad, M., Mayer, A., Czerkinsky, C., Holmgren, J., Thivolet, C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Treatment of experimental autoimmune encephalomyelitis by feeding myelin basic protein conjugated to cholera toxin B subunit. Sun, J.B., Rask, C., Olsson, T., Holmgren, J., Czerkinsky, C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting. Frey, A., Giannasca, K.T., Weltzin, R., Giannasca, P.J., Reggio, H., Lencer, W.I., Neutra, M.R. J. Exp. Med. (1996) [Pubmed]
  6. Lipid raft proteins have a random distribution during localized activation of the T-cell receptor. Glebov, O.O., Nichols, B.J. Nat. Cell Biol. (2004) [Pubmed]
  7. Analysis of structure and function of the B subunit of cholera toxin by the use of site-directed mutagenesis. Jobling, M.G., Holmes, R.K. Mol. Microbiol. (1991) [Pubmed]
  8. Structural basis for differential receptor binding of cholera and Escherichia coli heat-labile toxins: influence of heterologous amino acid substitutions in the cholera B-subunit. Bäckström, M., Shahabi, V., Johansson, S., Teneberg, S., Kjellberg, A., Miller-Podraza, H., Holmgren, J., Lebens, M. Mol. Microbiol. (1997) [Pubmed]
  9. Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood. Ahrén, C., Jertborn, M., Svennerholm, A.M. Infect. Immun. (1998) [Pubmed]
  10. Structural studies of receptor binding by cholera toxin mutants. Merritt, E.A., Sarfaty, S., Jobling, M.G., Chang, T., Holmes, R.K., Hirst, T.R., Hol, W.G. Protein Sci. (1997) [Pubmed]
  11. Interaction of a cholera toxin derivative containing a reduced number of receptor binding sites with intact cells in culture. De Wolf, M.J., Dams, E., Dierick, W.S. Biochim. Biophys. Acta (1994) [Pubmed]
  12. Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. Lykidis, A., Murti, K.G., Jackowski, S. J. Biol. Chem. (1998) [Pubmed]
  13. Fusion proteins containing the A2 domain of cholera toxin assemble with B polypeptides of cholera toxin to form immunoreactive and functional holotoxin-like chimeras. Jobling, M.G., Holmes, R.K. Infect. Immun. (1992) [Pubmed]
  14. A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes. Arakawa, T., Yu, J., Chong, D.K., Hough, J., Engen, P.C., Langridge, W.H. Nat. Biotechnol. (1998) [Pubmed]
  15. Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. Janes, P.W., Ley, S.C., Magee, A.I. J. Cell Biol. (1999) [Pubmed]
  16. Cell membrane GM1 ganglioside is a functional coreceptor for fibroblast growth factor 2. Rusnati, M., Urbinati, C., Tanghetti, E., Dell'Era, P., Lortat-Jacob, H., Presta, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann-Pick C1-deficient cells. Sugimoto, Y., Ninomiya, H., Ohsaki, Y., Higaki, K., Davies, J.P., Ioannou, Y.A., Ohno, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  18. Novel carbohydrate binding site recognizing blood group A and B determinants in a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits. Angström, J., Bäckström, M., Berntsson, A., Karlsson, N., Holmgren, J., Karlsson, K.A., Lebens, M., Teneberg, S. J. Biol. Chem. (2000) [Pubmed]
  19. Transcytosis of cholera toxin subunits across model human intestinal epithelia. Lencer, W.I., Moe, S., Rufo, P.A., Madara, J.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  20. Ganglioside GM1 binding toxins and human neuropathy-associated IgM antibodies differentially promote neuritogenesis in a PC12 assay. O'Hanlon, G.M., Hirst, T.R., Willison, H.J. Neurosci. Res. (2003) [Pubmed]
  21. Increased expression of cytosolic chaperonin CCT in human hepatocellular and colonic carcinoma. Yokota, S., Yamamoto, Y., Shimizu, K., Momoi, H., Kamikawa, T., Yamaoka, Y., Yanagi, H., Yura, T., Kubota, H. Cell Stress Chaperones (2001) [Pubmed]
  22. Characterization of the cytoplasmic chaperonin containing TCP-1 from the Antarctic fish Notothenia coriiceps. Pucciarelli, S., Parker, S.K., Detrich, H.W., Melki, R. Extremophiles (2006) [Pubmed]
  23. Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4+ regulatory T-cells. Ploix, C., Bergerot, I., Durand, A., Czerkinsky, C., Holmgren, J., Thivolet, C. Diabetes (1999) [Pubmed]
  24. Cooperativity of ganglioside-dependent with protein-dependent substratum adhesion and neurite extension of human neuroblastoma cells. Mugnai, G., Culp, L.A. Exp. Cell Res. (1987) [Pubmed]
  25. Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans. Rudin, A., Johansson, E.L., Bergquist, C., Holmgren, J. Infect. Immun. (1998) [Pubmed]
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