Disease relevance of MAZ

• These findings suggest epitope spreading between the Tr antigen and the MAZ-DCC complex and offer a possible model of immune-mediated cerebellar disease [1].
• In neuronal cells, MAZ interacts with DCC (Deleted in Colorectal Cancer product), the receptor for netrin-1, a neuronal survival factor [1].
• Probing a cerebellar expression library with TrAb sera from patients with Hodgkin's disease and paraneoplastic cerebellar degeneration resulted in the isolation of MAZ (myc-associated zinc-finger protein) [1].
• Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis [2].
• Inflammation-responsive transcription factor, serum amyloid A-activating factor 1 (SAF-1), has been shown to regulate several genes, including serum amyloid A, gamma-fibrinogen, and matrix metalloproteinase 1, whose abnormal expression is associated with the pathogenesis of arthritis, atherosclerosis, and amyloidosis [3].

Psychiatry related information on MAZ

• By immunoblot analysis, FAC1 and ZF87/MAZ exhibit similar tissue distribution and co-localize to pathologic structures in Alzheimer's disease brain [4].

High impact information on MAZ

• In contrast, pausing of Pol II elongation induced by a high-affinity DNA-binding protein does not activate polyadenylation, indicating that G-rich MAZ sequences have a specific effect on polyadenylation [5].
• The zinc finger protein MAZ, originally identified as a factor that binds to the c-myc P2 promoter, is associated with transcriptional termination [6].
• Cloned MAZ was used to obtain a consensus binding site, G5AG5 [6].
• The g11 and IgM MAZ sites lie within sequences that have activity in a termination assay and, furthermore, mutation of C2 or g11 MAZ sites severely reduces termination activity [6].
• The MAZ consensus sequence will facilitate the identification of further sites [6].

Chemical compound and disease context of MAZ

• Selenite supplementation decreases expression of MAZ in HT29 human colon adenocarcinoma cells [7].

Biological context of MAZ

• Human genes for KNSL4 and MAZ are located close to one another on chromosome 16p11.2 [8].
• We isolated genomic DNA clones that encoded KNSL4 and MAZ from a human cosmid library [8].
• The gene for KNSL4 spanned 16 kb and consisted of 14 exons and 13 introns, while the gene for MAZ spanned 6 kb and consisted of 5 exons and 4 introns [8].
• Three of the four MAZ binding sites also were shown to interact with transcription factor Sp1 [9].
• Overproduction of MAZ or Sp1 in transient transfection assays increased expression directed by the human 5'-flanking sequence, although MAZ was substantially more effective [9].

Anatomical context of MAZ

• Purified MAZ antibodies reacted with Purkinje cells [1].
• Moreover, the mutated MAZ was unable to enhance the expression of luciferase encoded by a c-myc promoter/luciferase reporter gene in HeLa cells in the presence of CKII [10].
• SAF-1 activity was detected in the chondrocytes of OA cartilage, where most of the cells stained positive for SAF-1 [2].
• CONCLUSION: The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients [2].
• Our results suggest that a distinct member of the MAZ family is expressed in human islet cells and enhances the transcriptional activity of the c-myc gene [11].

Associations of MAZ with chemical compounds

• The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1 [9].
• FAC1, on the other hand, recognizes a conformational interface that includes the proline/alanine-rich domain of ZF87/MAZ and the first zinc finger [4].
• Site-specific mutagenesis of MAZ revealed that the serine residue at position 480 was the major site of phosphorylation by CKII both in vitro and in vivo [10].
• When expressed as a fusion protein in a pMAL-c vector, MAZ binds with specificity to a GA box sequence (GGGAGGG) found in the c-MYC P2 promoter, to the P2 attenuator region within the gene's first exon, and to a related sequence involved in the transcriptional termination of the C2 gene [12].
• An S1 nuclease protection assay demonstrated the presence of multiple sites for initiation of transcription around a site 174 nucleotides (nt) upstream of the ATG codon and such expression was reflected by the promoter activity of a MAZ promoter/CAT (chloramphenicol acetyltransferase) reporter gene [13].

Physical interactions of MAZ

• Phosphorylation of MAZ by CKII at this serine residue was required for maximum binding of MAZ to the pyrimidine-rich DNA of the nuclease-hypersensitive element (NHE) in the 5'-end promoter region of the c-myc gene [10].
• Taken together, our studies suggest that the putative -45 to -39 MAZ-binding site regulates the constitutive activity of human PTHR1 P2 promoter [14].
• A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter [15].

Regulatory relationships of MAZ

• The data also demonstrate that control of SAF-1 activity can suppress induced expression of MMP-1 [2].
• We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene [15].
• Together these data indicate that SAF-1 controls cell cycle progression via p21 induction, and pathophysiological conditions that favor overexpression of SAF-1, such as an acute inflammatory condition, can trigger cellular growth arrest [3].
• The results indicate that telomerase has been activated in the course of SAF-1 development, and the highest levels of telomerase activity correlate with an increase in cell proliferation, thus supporting a permanent cell line [16].

Other interactions of MAZ

• Coexpression of FAC1 and ZF87/MAZ suggest that interaction of these two proteins will have biological implications for gene regulation in neurodegeneration [4].
• The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic cerebellar dysfunction [1].
• The DNA-binding and transcriptional activities of MAZ, a myc-associated zinc finger protein, are regulated by casein kinase II [10].
• Finally, ribonuclease protection assays showed that P2-specific PTHR1 mRNA transcript expression was significantly decreased in SaOS-2 cells transfected with ds-MAZ-oligo as compared with that for control (P<0.001) and ds-Sp1-oligo (P<0.05) [14].
• Assays of DNA binding and promoter activity of three exemplary motifs (ETS, CREB, and SP1/MAZ) were used to prove the effectiveness of SPCM in uncovering active sequences [17].

Analytical, diagnostic and therapeutic context of MAZ

• An immunofluorescence study demonstrated that DCC protein is expressed at elevated levels in neuron-like P19 EC cells, in particular in axons, in which the MAZ protein is also expressed [18].
• Electrophoretic mobility shift assays using SaOS-2 nuclear extracts and a double-stranded DNA fragment encompassing the -45 to -39 putative MAZ site (ds-MAZ-oligo) disclosed two specific DNA-protein complexes [14].
• Using chromatin immunoprecipitation, we show that MAZ binds the RAG-2 promoter region in pre-B cells [19].
• Microarray analysis for cell cycle-specific genes in SAF1-transfected cells identified several candidate genes whose expression levels were altered during SAF-1 overexpression [3].
• When a duplicate Northern blot was probed with a 300-bp fragment from the open reading frame of an MAZ cDNA clone, signal intensity was 2.2 times greater in Se- than in Se+ lanes [7].

References