Sequence-variant repeats of MUC1 show higher conformational flexibility, are less densely O-glycosylated and induce differential B lymphocyte responses

Glycobiology

Volumn 15, Issue 8, 2005, Pages 735-746

  von Mensdorff Pouilly, Silvia ^a   Kinarsky, Leo ^b   Engelmann, Katja ^c   Baldus, Stephan E ^c   Verheijen, René H ^a   Hollingsworth, Michael A ^b   Pisarev, Vladimir ^b   Sherman, Simon ^b   Hanisch, Franz Georg ^c  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^c UNIVERSITY OF COLOGNE   (Germany)

Author keywords

B cell response; Cancer; MUC1; O glycosylation; Peptide conformation

Indexed keywords

ALANINE; ARGININE; GLUTAMIC ACID; GLYCINE; GLYCOPEPTIDE; HISTIDINE; IMMUNOGLOBULIN G; MUCIN 1; N ACETYLGALACTOSAMINYLTRANSFERASE; OXYGEN; POLYPEPTIDE; PROLINE; SERINE; THREONINE; VALINE; CA 15-3 ANTIGEN; IMMUNOGLOBULIN M; POLYPEPTIDE N ACETYLGALACTOSAMINYLTRANSFERASE; POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; RECOMBINANT PROTEIN;

AMINO ACID SUBSTITUTION; ARTICLE; B LYMPHOCYTE ACTIVATION; BINDING AFFINITY; BREAST ADENOCARCINOMA; CELL STRAIN HEK293; CLINICAL ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; FEMALE; GENE SEQUENCE; GENETIC TRANSFECTION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; HUMORAL IMMUNITY; IN VITRO STUDY; IN VIVO STUDY; MALE; MASS SPECTROMETRY; NONHUMAN; OVARY ADENOCARCINOMA; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN GLYCOSYLATION; STOMACH ADENOCARCINOMA; ANIMAL; B LYMPHOCYTE; BREAST TUMOR; CHEMISTRY; COMPARATIVE STUDY; GENETICS; GLYCOSYLATION; IMMUNOLOGY; METABOLISM; MOUSE; NUCLEAR MAGNETIC RESONANCE; NUCLEOTIDE REPEAT; OVARY TUMOR; PATHOLOGY; STOMACH TUMOR;

ANIMALS; B-LYMPHOCYTES; BREAST NEOPLASMS; CA-15-3 ANTIGEN; FEMALE; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; MALE; MICE; N-ACETYLGALACTOSAMINYLTRANSFERASES; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; OVARIAN NEOPLASMS; PROTEIN CONFORMATION; RECOMBINANT PROTEINS; REPETITIVE SEQUENCES, NUCLEIC ACID; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; STOMACH NEOPLASMS;

EID: 25144456565     PISSN: 09596658     EISSN: 14602423     Source Type: Journal    
DOI: 10.1093/glycob/cwi058     Document Type: Article

References (25)

1. Croce, M.V., Isla-Larrain, M.T., Capafons, A., Price, M.R., and Segal-Eiras, A. (2001) Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women. Breast Cancer Res. Treat., 69, 1-11.
2. Engelmann, K., Baldus, S.E., and Hanisch, F.-G. (2001) Identification and topology of variant sequences within individual repeat domains of the human epithelial tumor mucin MUC1. J. Biol. Chem., 276, 27764-27769.
3. Fowler, J.C., Teixeira, A.S., Vinall, L.E., and Swallow, D.M. (2003) Hypervariability of the membrane-associated mucin and cancer marker MUC1. Hum. Genet., 113, 473-479.
4. Gendler, S., Lancaster, C.A., Taylor-Papadimitriou, J., Duhig, T., Peat, N., Burchell, J., Pemberton, L., Lalani, E.N., and Wilson, D. (1990) Molecular cloning and expression of the human tumor-associated polymorphic epithelial mucin PEM. J. Biol. Chem., 265, 15286-15293.
5. Güntert, P., Mumenthaler, C., and Wüthrich, K. (1997) Torsion angle dynamics for NMR structure calculation with the new program DYANA. J. Mol. Biol., 273, 283-298.
6. Hanisch, F.-G., Reis, C.A., Clausen, H., and Paulsen, H. (2001) Evidence for glycosylation-dependent activity of polypeptide N acetylgalactosaminyl-transferases rGalNAc-T2 and-T4 on mucin glycopeptides. Glycobiology, 11, 731-740.
7. Hanisch, F.-G., Schwientek, T., von Bergwelt-Baildon, M.S., Schultze, J.L., and Finn, O.J. (2003) O-Linked glycans control glycoprotein processing by antigen-presenting cells: A biochemical approach to the molecular aspects of MUC1 processing by dendritic cells. Eur. J. Immunol., 33(3242-32), 54.
8. Hiltbold, E.M., Alter, M.D., Ciborowski, P., and Finn, O.J. (1999) Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken up by dendritic cells. Cell Immunol., 194, 143-149.
9. Hiltbold, E.M., Vlad, A.M., Ciborowski, P., Watkins, S.C., and Finn, O.J. (2000) The mechanism of unresponsiveness to circulating tumor antigen MUC1 is a block in intracellular sorting and processing by dendritic cells. J. Immunol., 165, 3730-3741.
10. Karsten, U., Diotel, C., Klich, G., Paulsen, H., Goletz, S., Müller, S., and Hanisch, F.-G. (1998) Enhanced binding of antibodies to the DTR motif of MUC1 tandem repeat peptide is mediated by site-specific glycosylation. Cancer Res., 58, 2541-25490.
11. Kinarsky, L., Suryanarayanan, G., Prakash, O., Paulsen, H., Clausen, H., Hanisch, F.-G., Hollingsworth, M.A., and Sherman, S. (2003) Conformational studies on the MUC1 tandem repeat glycopeptides: implication for the enzy-matic O-glycosylation of the mucin protein core. Glycobiology, 13, 929-939.
12. Kirnarsky, L., Prakash, O., Vogen, S., Nomot, O.M., Hollingsworth, M.A., and Sherman, S. (2000) Structural effects of O-glycosylation on a, 15-residue peptide from the mucin (MUC1) core protein. Biochemistry 39, 12076-12082.
13. Lan, M.S., Batra, S.K., Qui, W.-N., Metzgar, R.S., and Hollingsworth, M.A. (1990) Cloning and sequencing of a human pancreatic tumor mucin cDNA. J. Biol. Chem., 265, 15294-15299.
14. Ligtenberg, M.J., Vos, H.L., Gennissen, A.M.C., and Hilkens, J. (1990) Episialin, a carcinoma associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. J. Biol. Chem., 265, 5573-5578.
15. von Mensdorff-Pouilly, S., Gourevitch, M.M., Kenemans, P., Verstraeten, A.A., Van Kamp, G.J., Kok, A., van Uffelen, K., Snijdewint, F.G., Paul, M.A., Meijer, S., and Hilgers, J. (1996) An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1). Tumor Biol., 19, 186-195.
16. von Mensdorff-Pouilly, S., Verstraeten, A.A., Kenemans, P., Snijdewint, F.G.M., Kok, A., Van Kamp, G.J., Paul, M.A., Van Diest, P.J., Meijer, S., and Hilgers, J. (2000a) Survival in early breast cancer patients is influenced by a natural humoral immune response to polymorphic epithelial mucin (MUC1). J. Clin. Oncol., 18, 574-583.
17. von Mensdorff-Pouilly, S., Petrakou, E., Kenemans, P., van Uffelen, K., Verstraeten, A.A., Snijdewint, F.G.M., van Kamp, G.J., Schol, D.J., Reis, C.A., Price, M.R., and others (2000b) Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and GalNAc peptides. Int. J. Cancer, 86, 702-712.
18. Müller, S., Alving, K., Peter-Katalinic, J., Zachara, N., Gooley, A.A., and Hanisch, F.-G. (1999) High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells. J. Biol. Chem., 274, 18165-18172.
19. Müller, S., Goletz, S., Packer, N., Gooley, A.A., Lawson, A.M., and Hanisch, F.-G. (1997) Localization of O-glycosylation sites on glycopeptide fragments from lactation-associated MUC1. J. Biol. Chem. 272, 24780-24793.
20. Müller, S., and Hanisch, F.-G. (2002) Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. J. Biol. Chem., 277, 26103-26112.
21. Price, M.R., Rye, P.D., and, 59 coauthors. (1998) Summary report on the ISOBM TD-4 Workshop: Analysis of 56 monoclonal antibodies against the MUC1 mucin. Tumor Biol. 19 (Suppl. 1), 120.
22. Sutherlin, M.E., Nishimori, I., Caffrey, T., Bennett, E.P., Hassan, H., Mandel, U., Mack, D., Iwamura, T., Clausen, H., and Hollingsworth, M.A. (1997) Expression of three UDP-GalNAc: Polypeptide GalNAc N acetylgalactosaminyltransferases in adenocarcinoma cell lines. Cancer Res., 57, 4744-4748.
23. Vlad, A.M., Muller, S., Cudic, M., Paulsen, H., Otvos, L., Hanisch, F.-G., and Finn, O.J. (2002) Complex carbohydrates are not removed during processing of glycoproteins by dendritic cells: Processing of tumor antigen MUC1 glycopeptides for presentation to major histocompatibility complex class II-restricted T cells. J. Exp. Med. 196, 1435-1446.
24. Wreschner, D.H., Hareuveni, M., Tsarfaty, I., Smorodinky, N., Horev, J., Zaretzky, J., Kotkes, P., Weiss, M., Lathe, R., and Dion, A. (1990) Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms. Eur. J. Biochem., 189, 463-473.
25. Wüthrich, K. NMR of Proteins and Nucleic Acids. John Wiley and Sons, New York (1986).