Alternative titles; symbols
HGNC Approved Gene Symbol: MNT
Cytogenetic location: 17p13.3 Genomic coordinates (GRCh38): 17:2,384,073-2,401,060 (from NCBI)
Proteins of the MYC (190080) and MAD (600021) family are involved in transcriptional regulation and mediate cell differentiation and proliferation. These molecules share a basic helix-loop-helix leucine zipper domain (bHLHZip) and bind DNA at the E box (CANNTG) consensus by forming heterodimers with MAX (154950). MYC-MAX complexes activate transcription, while MAD-MAX complexes repress transcription through recruitment of the SIN3 corepressor (see 607776). Meroni et al. (1997) identified the human ROX gene, a new member of the bHLHZip family, as a transcribed sequence from 17p13.3 and isolated human fetal brain ROX cDNAs. The deduced 582-amino acid human ROX protein shares 88.5% identity with the 591-amino acid mouse Rox. In vitro translated ROX protein has a molecular mass of 70 kD. The authors showed that ROX is a nuclear protein that heterodimerizes with MAX and binds the E box with its bHLHZip domain. ROX repressed transcription in both human HEK293 cells and yeast; repression in yeast was through interaction between its N terminus and the Sin3 corepressor. The authors demonstrated that ROX is highly expressed in quiescent fibroblasts and that expression is decreased when cells enter the cell cycle. Northern blot analysis detected a 4.8-kb ROX transcript in all human tissues examined.
By searching for proteins that interact with Max in a yeast 2-hybrid system, Hurlin et al. (1997) isolated mouse cDNAs encoding Mnt. They found that Mnt-Max heterodimers act as transcriptional repressors of E box promoters and that repression by Mnt maps to the Sin3-interaction domain (SID). Wildtype Mnt suppressed Myc+Ras cotransformation of primary cells, while a Mnt protein containing a SID deletion cooperated with Ras in the absence of Myc to transform cells. Hurlin et al. (1997) detected expression of Mnt mRNA in both proliferating and differentiating cells, and in a wide range of embryonic cell types together with Nmyc (164840) and Myc mRNAs. They also found that Mnt-Max and Myc-Max heterocomplexes coexist in proliferating cell populations. Transgenic mice expressing Mnt under the control of the beta-actin (102630) promoter exhibited a delay in development and appeared to die between days 8.5 and 10.5 of gestation.
Lo Nigro et al. (1998) determined that the human ROX gene contains 6 exons and spans less than 40 kb. Using single-stranded conformational polymorphism analysis of the ROX coding region in 16 sporadic breast cancers showing loss of heterozygosity at 17p13.3, they were unable to find mutations in the nondeleted allele of ROX. Polymorphic proteins identified in this study showed no significant decreases in their abilities to bind DNA or to repress transcription.
Meroni et al. (1997) identified the human ROX gene as a transcribed sequence from chromosome 17p13.3. They mapped the mouse Rox gene to chromosome 11, in a region showing homology of synteny with the location of the human ROX gene.
Toyo-oka et al. (2004) produced knockout mice for MAX-binding protein (Mnt). Virtually all homozygote mutants in a mixed (129S6 x NIH Black Swiss) or inbred (129S6) genetic background died perinatally. Mnt-deficient embryos exhibited small size throughout development and showed reduced levels of c-Myc (190080) and N-Myc (164840). In addition, 37% of mixed-background mutants displayed cleft palate as well as retardation of skull development, a phenotype not observed in the inbred mutants. The authors proposed an important role for Mnt in embryonic development and survival, and suggested that Mnt may play a role in the craniofacial defects displayed by patients with Miller-Dieker syndrome (247200).
Hurlin, P. J., Queva, C., Eisenman, R. N. Mnt, a novel Max-interacting protein is coexpressed with Myc in proliferating cells and mediates repression at Myc binding sites. Genes Dev. 11: 44-58, 1997. [PubMed: 9000049] [Full Text: https://doi.org/10.1101/gad.11.1.44]
Lo Nigro, C., Venesio, T., Reymond, A., Meroni, G., Alberici, P., Cainarca, S., Enrico, F., Stack, M., Ledbetter, D. H., Liscia, D. S., Ballabio, A., Carrozzo, R. The human ROX gene: genomic structure and mutation analysis in human breast tumors. Genomics 49: 275-282, 1998. [PubMed: 9598315] [Full Text: https://doi.org/10.1006/geno.1998.5241]
Meroni, G., Reymond, A., Alcalay, M., Borsani, G., Tanigami, A., Tonlorenzi, R., Lo Nigro, C., Messali, S., Zollo, M., Ledbetter, D. H., Brent, R., Ballabio, A., Carrozzo, R. 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. EMBO J. 16: 2892-2906, 1997. Note: Erratum: EMBO J. 16: 6055 only, 1997. [PubMed: 9184233] [Full Text: https://doi.org/10.1093/emboj/16.10.2892]
Toyo-oka, K., Hirotsune, S., Gambello, M. J., Zhou, Z.-Q., Olson, L., Rosenfeld, M. G., Eisenman, R., Hurlin, P., Wynshaw-Boris, A. Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller-Dieker syndrome. Hum. Molec. Genet. 13: 1057-1067, 2004. [PubMed: 15028671] [Full Text: https://doi.org/10.1093/hmg/ddh116]