Alternative titles; symbols
HGNC Approved Gene Symbol: MAZ
Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38): 16:29,806,124-29,811,164 (from NCBI)
The c-Myc protooncogene (190080) encodes a nuclear phosphoprotein involved in malignant tumorigenesis. The MYC gene product functions as a DNA-specific transcription factor. A related polypeptide called MAX (154950), for MYC-associated factor X, dimerizes with MYC to optimize DNA binding. A paucity of negative regulatory elements have been reported for the MYC gene which regulate transcription from 2 initiation sites specified by the P1 and P2 promoters. ME1a1, a 16-bp nuclear nuclear factor binding site residing between MYC P1 and P2 transcription initiation sites, is required for P2 activity. Bossone et al. (1992) cloned a cDNA encoding a 477-amino acid zinc finger protein, designated MAZ (MYC-associated zinc finger protein), from a HeLa cell cDNA library by screening with a concatamerized ME1a1 binding site probe. Its mRNA was present in all tissues tested (except kidney) as a doublet of approximately 2.5 to 2.7 kb, along with differentially expressed minor species. The authors speculated that MAZ may encode a transcription factor with dual roles in transcription initiation and termination.
Kennedy and Rutter (1992) cloned a full-length cDNA of Pur1 from a mouse islet cell line. By sequence analysis, they identified MAZ as the human homolog of mouse Pur1. The deduced hamster, mouse, and human proteins share approximately 94% sequence identity.
Tsutsui et al. (1996) used Southwestern methods to screen a human pancreatic islet cell cDNA library for genes encoding proteins that could bind specifically to the nuclease hypersensitive element of human c-myc. They identified a gene, named MAZi (for Myc-associated zinc finger protein of islet), which had a 497-bp open reading frame and was found to be 99.8% identical to MAZ. The only differences between MAZi and MAZ were a different 5-prime noncoding region and a shorter polyalanine tract (11 vs 16 alanines). Thus, MAZi is likely to be a product of the MAZ gene. However, Tsutsui et al. (1996) reported that the expression pattern and transcript size of MAZi differed from that of MAZ. The authors found that a 2.6-kb MAZi transcript was expressed at 5- to 10-fold higher levels in rat islet carcinoma cells than in normal rat islet cells and that transfection of islet cells with MAZi resulted in enhanced expression of a c-myc/reporter construct. The authors suggested that MAZi may be a positive factor that enhances the expression of c-myc in islet cells.
Kennedy and Rutter (1992) identified a transcription factor, which they referred to as Pur1 because of its ability to bind to purine-rich sequences, from a hamster insulinoma cell line. Such purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin (INS; 176730). Mutation analysis suggested that the GAGA box plays an important role in transcription of the rat insulin I gene. Kennedy and Rutter (1992) found that Pur1 binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Cotransfection experiments showed that Pur1 is a potent transactivator in both pancreatic and nonpancreatic cells. Pur1 was also found to stimulate transcription from the intact rat insulin I promoter in HeLa cells, where the promoter is normally inactive.
Song et al. (1998) showed that both MAZ protein and mRNA levels are modulated in a cell cycle-dependent manner.
Gastrin (GAS; 137250) regulates the expression of a variety of genes involved in the control of acid secretion. It also triggers tissue response to damage, infection, and inflammation in cells expressing gastrin receptor (CCKBR; 118445) and, indirectly, in nearby cells via a paracrine mechanism. Almeida-Vega et al. (2009) found that gastrin directly induced upregulation of the antiapoptotic regulator PAI2 (SERPINB2; 173390) in CCKBR-positive cells. CCKBR-positive cells also released IL8 (146930) and prostaglandin E2 into the culture medium in response to gastrin, which resulted in elevated PAI2 expression in cocultured CCKBR-negative cells. IL8 signaling in CCKBR-negative cells upregulated PAI2 via binding of the ASC1 complex (see TRIP4; 604501) to the PAI2 promoter. Prostaglandin E2 independently upregulated PAI2 via RHOA (165390)-dependent signaling that induced binding of MAZ to the PAI2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis revealed that MAZ and the p50 subunit of the ASC1 complex (ASCC1; 614215) bound directly to sites in the PAI2 promoter. Mutation of the putative MAZ site in the PAI2 promoter reduced responses to RHOA. Knockdown of the p50 or p65 (TRIP4) subunits of the ASC1 complex via small interfering RNA significantly reduced PAI2 upregulation in response to gastrin.
Song et al. (1998) found that the MAZ gene contains 5 exons and spans approximately 6 kb. The promoter region has features typical of a housekeeping gene. The authors identified regulatory elements in the 5-prime flanking sequence that are involved in basal transcription and in the autoregulation of the MAZ gene by the MAZ protein.
By fluorescence in situ hybridization, Song et al. (1998, 1998) mapped the MAZ gene to chromosome 16p11.2, within 1.2 kb of the KNLS4 (603213) gene.
Almeida-Vega, S., Catlow, K., Kenny, S., Dimaline, R., Varro, A. Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G414-G423, 2009. [PubMed: 19074642] [Full Text: https://doi.org/10.1152/ajpgi.90340.2008]
Bossone, S. A., Asselin, C., Patel, A. J., Marcu, K. B. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc. Nat. Acad. Sci. 89: 7452-7456, 1992. [PubMed: 1502157] [Full Text: https://doi.org/10.1073/pnas.89.16.7452]
Kennedy, G. C., Rutter, W. J. Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells. Proc. Nat. Acad. Sci. 89: 11498-11502, 1992. [PubMed: 1454839] [Full Text: https://doi.org/10.1073/pnas.89.23.11498]
Song, J., Murakami, H., Tsutsui, H., Tang, X., Matsumura, M., Itakura, K., Kanazawa, I., Sun, K., Yokoyama, K. K. Genomic organization and expression of a human gene for myc-associated zinc finger protein (MAZ). J. Biol. Chem. 273: 20603-20614, 1998. [PubMed: 9685418] [Full Text: https://doi.org/10.1074/jbc.273.32.20603]
Song, J., Murakami, H., Yang, Z. Q., Koga, C., Adati, N., Murata, T., Geltinger, C., Saito-Ohara, F., Ikeuchi, T., Matsumura, M., Itakura, K., Kanazawa, I., Sun, K., Yokoyama, K. K. Human genes for KNSL4 and MAZ are located close to one another on chromosome 16p11.2. Genomics 52: 374-377, 1998. [PubMed: 9790757] [Full Text: https://doi.org/10.1006/geno.1998.5452]
Tsutsui, H., Sakatsume, O., Itakura, K., Yokoyama, K. K. Members of the MAZ family: a novel cDNA clone for MAZ from human pancreatic islet cells. Biochem. Biophys. Res. Commun. 226: 801-809, 1996. [PubMed: 8831693] [Full Text: https://doi.org/10.1006/bbrc.1996.1432]