Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment

J. Pastorek, S. Pastorekova, I. Callebaut, J. P. Mornon, V. Zelnik, R. Opavsky, M. Zat'ovicova, S. Liao, D. Portetelle, E. J. Stanbridge, J. Zavada, A. Burny, R. Kettmann

Research output: Contribution to journalArticle

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Abstract

MN is a transmembrane glycoprotein that has been detected in HeLa cells and in some human carcinomas. The expression of MN protein in HeLa cells is regulated by cell density. In HeLa x fibroblast cell hybrids its expression correlates with tumorigenicity. Using a specific monoclonal antibody we have identified a cDNA clone coding for MN. Analysis of the deduced amino acid sequence revealed strong structural homology between the central region of the MN protein and carbonic anhydrases (CA). MN sequence retains the conserved zinc-binding site as well as the enzyme's active center. In accord with these findings, MN protein from HeLa cells was found to bind zinc and to have carbonic anhydrase activity. The N-terminal region of MN shares some similarity with DNA binding proteins of the helix-loop-helix (HLH) family, and the protein was found to have affinity for DNA by DNA-cellulose chromatography. The region between the CA-like domain and the putative HLH domain is rich in imperfect repeats of serine, proline, glycine and acidic residues with few hydrophobic amino acids, resembling thus an activation region of transcription factors. The fact that MN protein is detectable in several types of human carcinomas, but not in corresponding non-cancerous tissues, suggests its possible role in neoplasia. In addition, the analysis of biological consequences of MN expression of NIH3T3 cells provides the evidence in favour of MN protein involvement in control of cell proliferation and transformation.

Original languageEnglish (US)
Pages (from-to)2877-2888
Number of pages12
JournalOncogene
Volume9
Issue number10
StatePublished - Jan 1 1994

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Carbonic Anhydrases
Organism Cloning
DNA
HeLa Cells
Neoplasms
Proteins
Zinc
Helix-Loop-Helix Motifs
Carcinoma
Hybrid Cells
Conserved Sequence
Protein Sequence Analysis
DNA-Binding Proteins
Proline
Glycine
Serine
Chromatography
Glycoproteins
Transcription Factors
Complementary DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Pastorek, J., Pastorekova, S., Callebaut, I., Mornon, J. P., Zelnik, V., Opavsky, R., ... Kettmann, R. (1994). Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Oncogene, 9(10), 2877-2888.

Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. / Pastorek, J.; Pastorekova, S.; Callebaut, I.; Mornon, J. P.; Zelnik, V.; Opavsky, R.; Zat'ovicova, M.; Liao, S.; Portetelle, D.; Stanbridge, E. J.; Zavada, J.; Burny, A.; Kettmann, R.

In: Oncogene, Vol. 9, No. 10, 01.01.1994, p. 2877-2888.

Research output: Contribution to journalArticle

Pastorek, J, Pastorekova, S, Callebaut, I, Mornon, JP, Zelnik, V, Opavsky, R, Zat'ovicova, M, Liao, S, Portetelle, D, Stanbridge, EJ, Zavada, J, Burny, A & Kettmann, R 1994, 'Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment', Oncogene, vol. 9, no. 10, pp. 2877-2888.
Pastorek, J. ; Pastorekova, S. ; Callebaut, I. ; Mornon, J. P. ; Zelnik, V. ; Opavsky, R. ; Zat'ovicova, M. ; Liao, S. ; Portetelle, D. ; Stanbridge, E. J. ; Zavada, J. ; Burny, A. ; Kettmann, R. / Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. In: Oncogene. 1994 ; Vol. 9, No. 10. pp. 2877-2888.
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abstract = "MN is a transmembrane glycoprotein that has been detected in HeLa cells and in some human carcinomas. The expression of MN protein in HeLa cells is regulated by cell density. In HeLa x fibroblast cell hybrids its expression correlates with tumorigenicity. Using a specific monoclonal antibody we have identified a cDNA clone coding for MN. Analysis of the deduced amino acid sequence revealed strong structural homology between the central region of the MN protein and carbonic anhydrases (CA). MN sequence retains the conserved zinc-binding site as well as the enzyme's active center. In accord with these findings, MN protein from HeLa cells was found to bind zinc and to have carbonic anhydrase activity. The N-terminal region of MN shares some similarity with DNA binding proteins of the helix-loop-helix (HLH) family, and the protein was found to have affinity for DNA by DNA-cellulose chromatography. The region between the CA-like domain and the putative HLH domain is rich in imperfect repeats of serine, proline, glycine and acidic residues with few hydrophobic amino acids, resembling thus an activation region of transcription factors. The fact that MN protein is detectable in several types of human carcinomas, but not in corresponding non-cancerous tissues, suggests its possible role in neoplasia. In addition, the analysis of biological consequences of MN expression of NIH3T3 cells provides the evidence in favour of MN protein involvement in control of cell proliferation and transformation.",
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T1 - Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment

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AU - Pastorekova, S.

AU - Callebaut, I.

AU - Mornon, J. P.

AU - Zelnik, V.

AU - Opavsky, R.

AU - Zat'ovicova, M.

AU - Liao, S.

AU - Portetelle, D.

AU - Stanbridge, E. J.

AU - Zavada, J.

AU - Burny, A.

AU - Kettmann, R.

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N2 - MN is a transmembrane glycoprotein that has been detected in HeLa cells and in some human carcinomas. The expression of MN protein in HeLa cells is regulated by cell density. In HeLa x fibroblast cell hybrids its expression correlates with tumorigenicity. Using a specific monoclonal antibody we have identified a cDNA clone coding for MN. Analysis of the deduced amino acid sequence revealed strong structural homology between the central region of the MN protein and carbonic anhydrases (CA). MN sequence retains the conserved zinc-binding site as well as the enzyme's active center. In accord with these findings, MN protein from HeLa cells was found to bind zinc and to have carbonic anhydrase activity. The N-terminal region of MN shares some similarity with DNA binding proteins of the helix-loop-helix (HLH) family, and the protein was found to have affinity for DNA by DNA-cellulose chromatography. The region between the CA-like domain and the putative HLH domain is rich in imperfect repeats of serine, proline, glycine and acidic residues with few hydrophobic amino acids, resembling thus an activation region of transcription factors. The fact that MN protein is detectable in several types of human carcinomas, but not in corresponding non-cancerous tissues, suggests its possible role in neoplasia. In addition, the analysis of biological consequences of MN expression of NIH3T3 cells provides the evidence in favour of MN protein involvement in control of cell proliferation and transformation.

AB - MN is a transmembrane glycoprotein that has been detected in HeLa cells and in some human carcinomas. The expression of MN protein in HeLa cells is regulated by cell density. In HeLa x fibroblast cell hybrids its expression correlates with tumorigenicity. Using a specific monoclonal antibody we have identified a cDNA clone coding for MN. Analysis of the deduced amino acid sequence revealed strong structural homology between the central region of the MN protein and carbonic anhydrases (CA). MN sequence retains the conserved zinc-binding site as well as the enzyme's active center. In accord with these findings, MN protein from HeLa cells was found to bind zinc and to have carbonic anhydrase activity. The N-terminal region of MN shares some similarity with DNA binding proteins of the helix-loop-helix (HLH) family, and the protein was found to have affinity for DNA by DNA-cellulose chromatography. The region between the CA-like domain and the putative HLH domain is rich in imperfect repeats of serine, proline, glycine and acidic residues with few hydrophobic amino acids, resembling thus an activation region of transcription factors. The fact that MN protein is detectable in several types of human carcinomas, but not in corresponding non-cancerous tissues, suggests its possible role in neoplasia. In addition, the analysis of biological consequences of MN expression of NIH3T3 cells provides the evidence in favour of MN protein involvement in control of cell proliferation and transformation.

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