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Gene Review

MNT  -  MAX network transcriptional repressor

Homo sapiens

Synonyms: BHLHD3, Class D basic helix-loop-helix protein 3, MAD6, MXD6, Max-binding protein MNT, ...
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Disease relevance of MNT

  • Moreover, ROX expression appears to be induced in U937 myeloid leukemia cells stimulated to differentiate with 12-O-tetradecanoylphorbol-13-acetate [1].
  • The human ROX gene: genomic structure and mutation analysis in human breast tumors [2].
  • Moreover, the relative expression of MYC to ROX/MNT was increased in 4 of the 14 medulloblastomas [3].
  • The NS3P expression showed a significant correlation with the presence of cirrhosis, chronic active hepatitis (CAH) and tumor grade (P < 0.05). c-erbB2 overexpression and p21(waf) loss were higher in MNT than in HCC patients, however, this did not reach a statistically significant level [4].
  • Despite an extensive search for alterations in 52 lung cancer specimens. somatic mutations of ROX/Mnt could not be identified [5].

High impact information on MNT

  • Furthermore, mapping of the human gene to chromosome 17p13.3 in a region that frequently undergoes loss of heterozygosity in a number of malignancies, together with the biochemical and expression features, suggest involvement of ROX in human neoplasia [1].
  • ROX is highly expressed in quiescent fibroblasts and expression markedly decreases when cells enter the cell cycle [1].
  • MNT, a MAX-binding antagonist of c-MYC function, was up-regulated, implying a negative feedback loop [6].
  • MNT maps to human chromosome 17p13.3, a region frequently deleted in various human tumors, including mammary gland tumors [7].
  • A chip design that can perform both pressure and electrokinetic (EK) injection is described, and a mixture of fluorescein and ROX dyes in borate buffer is utilized as a model sample system [8].

Chemical compound and disease context of MNT


Biological context of MNT

  • In vitro translated assays did not show a significant decrease in the ability of the ROX mutant proteins to bind DNA or to repress transcription of a driven reporter gene in HEK293 cells [2].
  • Despite experimental evidence that ROX might act as a tumor suppressor gene, our data suggest that mutations in the coding region of ROX are uncommon in human breast tumorigenesis [2].
  • Here we report the genomic structure of the human ROX gene, which is composed of six exons and spans a genomic region of less than 40 kb [2].
  • These biological properties of ROX suggest a possible involvement of this gene in cell proliferation and differentiation [2].
  • Five nucleotide polymorphisms were identified in the ROX gene, three of which caused an amino acid substitution [2].

Anatomical context of MNT

  • ROX is capable of heterodimerizing with Max and acts as a transcriptional repressor in an E-box-driven reporter gene system, while it was found to activate transcription in HeLa cells [2].
  • In this study, we analyzed MNT mRNA and protein expression in 44 MB samples, including 32 primary tumors, 3 recurrent tumors and 9 MB cell lines [11].
  • In order to evaluate the correlation between the in vitro micronucleus assay (MNT) and the in vitro chromosome aberration test (CA), we collected data from four pharmaceutical companies obtained either in Chinese hamster cell lines (CHO-K5, CHO-K1, V79) or in human peripheral blood lymphocytes [12].
  • In the mouse bone marrow micronucleus (MNT), there were no significant increases in micronucleated polychromatic erythrocytes (with evaluation of 2000/animal), after treatment with 0.5, 1, and 2 g/kg/day CS-1246 (6/dose group) for 2 consecutive days and sacrifice 24 h later [13].
  • Cytokinesis-blocked micronucleus assay (MNT) was applied in the peripheral blood lymphocytes of patients undergoing radioiodine-131 ((131)I) therapy for differentiated thyroid carcinoma (DTC) after thyroidectomy to assess the genotoxic risk of this therapy [14].

Associations of MNT with chemical compounds

  • The EDA component of graphite-water adsorption for the acceptors correlated with the NMR-determined complexation constant with the model donors in chloroform, which, in turn, correlated with pi-acceptor strength (TNT > DNT > MNT > BNTL) and pi-donor strength (PYR > PHEN > NAPH) [15].
  • Since MNT results proved to be stable even during an illness episode, a possible link is suggested between personality traits and central serotonin metabolism [16].
  • Sorption of pi-acceptors, benzonitrile (BNTL), 4-nitrotoluene (MNT), 2,4-dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT), and to a lesser extent pi-donor solutes, naphthalene (NAPH) and phenanthrene (PHEN), was greater than predicted by hydrophobic driving forces in accord with their acceptor or donor strength [15].
  • Correlation structure between biological and psychological variables was homogeneous throughout the diagnoses and a significant inverse correlation was found only between CSF 5-HIAA and the validity factor of MNT [16].
  • Inhibition of iodotyrosine deiodination by treatment with 50 mumol MNT per day for 1 week caused a highly significant elevation of DIT serum levels to 4.80 +/- 3.30 nmol/l, a decrease of MCR to 9.0 ml/h . 100 g bw and a ten-fold increase of the DIT turnover rate to 43.2 pmol/h . 100 g bw [17].

Other interactions of MNT

  • We have recently isolated a human gene, ROX, encoding a new member of the basic helix-loop-helix leucine zipper protein family [2].
  • RESULTS: The NS3P expression was lower in HCC (65.6%) than in MNT (94.4%) patients [4].
  • Maximal TSH response to TRH stimulation correlated with both solidity and stability in the MNT scale [16].

Analytical, diagnostic and therapeutic context of MNT


  1. Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor. Meroni, G., Reymond, A., Alcalay, M., Borsani, G., Tanigami, A., Tonlorenzi, R., Nigro, C.L., Messali, S., Zollo, M., Ledbetter, D.H., Brent, R., Ballabio, A., Carrozzo, R. EMBO J. (1997) [Pubmed]
  2. The human ROX gene: genomic structure and mutation analysis in human breast tumors. Nigro, C.L., Venesio, T., Reymond, A., Meroni, G., Alberici, P., Cainarca, S., Enrico, F., Stack, M., Ledbetter, D.H., Liscia, D.S., Ballabio, A., Carrozzo, R. Genomics (1998) [Pubmed]
  3. Analysis of transcripts from 17p13.3 in medulloblastoma suggests ROX/MNT as a potential tumour suppressor gene. Cvekl, A., Zavadil, J., Birshtein, B.K., Grotzer, M.A., Cvekl, A. Eur. J. Cancer (2004) [Pubmed]
  4. Hepatitis C virus-NS3P in relation to p53, p21waf, mdm2, p21-ras and c-erbB2 in hepatocarcinogenesis. Bahnassi, A.A., Zekri, A.R., El-Houssini, S., Mokhtar, N.M., Abdel-Aziz, A.O., Sherif, G.M., El-Mishad, A.M., Khaled, H.M. J. Gastroenterol. Hepatol. (2005) [Pubmed]
  5. Molecular analysis of a Myc antagonist, ROX/Mnt, at 17p13.3 in human lung cancers. Takahashi, T., Konishi, H., Kozaki, K., Osada, H., Saji, S., Takahashi, T., Takahashi, T. Jpn. J. Cancer Res. (1998) [Pubmed]
  6. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Menssen, A., Hermeking, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression. Toyo-oka, K., Bowen, T.J., Hirotsune, S., Li, Z., Jain, S., Ota, S., Escoubet-Lozach, L., Lozach, L.E., Garcia-Bassets, I., Bassett, I.G., Lozach, J., Rosenfeld, M.G., Glass, C.K., Eisenman, R., Ren, B., Hurlin, P., Wynshaw-Boris, A. Cancer Res. (2006) [Pubmed]
  8. Pressure injection on a valved microdevice for electrophoretic analysis of submicroliter samples. Karlinsey, J.M., Monahan, J., Marchiarullo, D.J., Ferrance, J.P., Landers, J.P. Anal. Chem. (2005) [Pubmed]
  9. Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) as first-line therapy for patients with colorectal cancer. Yamada, Y., Ohtsu, A., Boku, N., Miyata, Y., Shimada, Y., Doi, T., Muro, K., Muto, M., Hamaguchi, T., Mera, K., Yano, T., Tanigawara, Y., Shirao, K. Jpn. J. Clin. Oncol. (2006) [Pubmed]
  10. Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes. Sasaki, M., Nakayama, M., Numazawa, S., Oguro, T., Honma, S., Iwamura, S., Tsukamoto, K., Yoshida, T. Arzneimittel-Forschung. (2001) [Pubmed]
  11. Analysis of the Max-binding protein MNT in human medulloblastomas. Sommer, A., Waha, A., Tonn, J., Sörensen, N., Hurlin, P.J., Eisenman, R.N., Lüscher, B., Pietsch, T. Int. J. Cancer (1999) [Pubmed]
  12. Comparative evaluation of the in vitro micronucleus test and the in vitro chromosome aberration test: industrial experience. Miller, B., Albertini, S., Locher, F., Thybaud, V., Lorge, E. Mutat. Res. (1997) [Pubmed]
  13. Mode of mutagenic action for the biocide Bioban CS-1246 in mouse lymphoma cells and implications for its in vivo mutagenic potential. Charles, G.D., Spencer, P.J., Schisler, M.R., Cifone, M., Budinsky, R.A., Gollapudi, B.B. Toxicol. Sci. (2005) [Pubmed]
  14. Cytokinesis-block micronucleus test in patients undergoing radioiodine therapy for differentiated thyroid carcinoma. Popova, L., Hadjidekova, V., Hadjieva, T., Agova, S., Vasilev, I. Hellenic journal of nuclear medicine. (2005) [Pubmed]
  15. Characterization of aromatic compound sorptive interactions with black carbon (charcoal) assisted by graphite as a model. Zhu, D., Pignatello, J.J. Environ. Sci. Technol. (2005) [Pubmed]
  16. Relationship between cerebrospinal fluid amine metabolites, neuroendocrine findings and personality dimensions (Marke-Nyman scale factors) in psychiatric patients. Banki, C.M., Arató, M. Acta psychiatrica Scandinavica. (1983) [Pubmed]
  17. Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat. Meinhold, H., Buchholz, R. Acta Endocrinol. (1983) [Pubmed]
  18. Personality changes in the aged. A longitudinal study with the MNT-scale. Nilsson, L.V., Persson, G. Acta psychiatrica Scandinavica. (1983) [Pubmed]
  19. MNT essential to plans for adding prescription drug benefit to Medicare. Larson, E. Journal of the American Dietetic Association. (2000) [Pubmed]
  20. Complementary/alternative medicine: another path to MNT coverage? Michalczyk, D. Journal of the American Dietetic Association. (2000) [Pubmed]
  21. Comparative study on antibody determination by different methods in sera of persons vaccinated with HDCS rabies vaccine. Kuwert, E.K., Thraenhart, O., Marcus, I., Werner, J., Atanasiu, P., Bahmanyar, M., Bögel, K., Cox, J.H., Schneider, L.G., Turner, G., Wiktor, T.J. Dev. Biol. Stand. (1978) [Pubmed]
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