Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the small Maf family (MafK, MafF, and MafG) are basic region leucine zipper (bZip) proteins that can function as transcriptional activators or repressors. The dimer compositions of their DNA binding forms determine whether the small Maf family proteins activate or repress transcription. Using a yeast two-hybrid screen with a GAL4-MafK fusion protein, we have identified two novel bZip transcription factors, Bach1 and Bach2, as heterodimerization partners of MafK. In addition to a Cap'n'collar-type bZip domain, these Bach proteins possess a BTB domain which is a protein interaction motif; Bach1 and Bach2 show significant similarity to each other in these regions but are otherwise divergent. Whereas expression of Bach1 appears ubiquitous, that of Bach2 is restricted to monocytes and neuronal cells. Bach proteins bind in vitro to NF-E2 binding sites, recognition elements for the hematopoietic transcription factor NF-E2, by forming heterodimers with MafK. Furthermore, a DNA binding complex that contained MafK as well as Bach2 or a protein related closely to Bach2 was found to be present in mouse brain cells. Bach1 and Bach2 function as transcription repressors in transfection assays using fibroblast cells, but they function as a transcriptional activator and repressor, respectively, in cultured erythroid cells. The results suggest that members of the Bach family play important roles in coordinating transcription activation and repression by MafK.
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PMID:Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. 888 38

The human TCF11 gene encodes a ubiquitously expressed bZIP transcription factor of the cap n' collar (CNC) domain family. It has a high sequence similarity to the erythroid-specific bZIP factor p45 NF-E2 in the CNC domain, which is involved in DNA binding. LCR-F1, a TCF11 isoform, is a more potent transcriptional activator than p45 NF-E2 in erythroid cells. We show here that the TCF11 protein interacts to form heterodimers with small Maf proteins, previously shown to dimerize with p45 NF-E2, ECH and Fos. Such heterodimerization significantly alters the DNA binding characteristics of TCF11. While TCF11 alone binds in vitro to the tandem NF-E2 site derived from 5' DNase hypersensitive site 2 in the beta-globin locus control region and to the single NF-E2 site in the porphobilinogen deaminase gene promoter, stronger binding is detected in the presence of small Maf proteins. Using antibodies, TCF11 isoforms bound to the single NF-E2 site were detected in K562 erythroid cell nuclear extracts. These findings place TCF11 as a good candidate for the proposed widely expressed factor(s) known to interact with small Maf proteins and bind NF-E2 sites in a sequence-specific manner resembling NF-E2.
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PMID:Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1. 893 85

The MafB transcriptional activator plays a pivotal role in regulating lineage-specific gene expression during hematopoiesis by repressing Ets-1-mediated transcription of key erythroid-specific genes in myeloid cells. To determine the effects of Maf family proteins on the transactivation of myeloid-specific genes in myeloid cells, we tested the ability of c-Maf to influence Ets-1- and c-Myb-dependent CD13/APN transcription. Expression of c-Maf in human immature myeloblastic cells inhibited CD13/APN-driven reporter gene activity (85 to 95% reduction) and required the binding of both c-Myb and Ets, but not Maf, to the promoter fragment. c-Maf's inhibition of CD13/APN expression correlates with its ability to physically associate with c-Myb. While c-Maf mRNA and protein levels remain constant during myeloid differentiation, formation of inhibitory Myb-Maf complexes was developmentally regulated, with their levels being highest in immature myeloid cell lines and markedly decreased in cell lines representing later developmental stages. This pattern matched that of CD13/APN reporter gene expression, indicating that Maf modulation of c-Myb activity may be an important mechanism for the control of gene transcription during hematopoietic cell development.
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PMID:c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation. 956 92

The MafB transcription factor plays a pivotal role in controlling the development and differentiation. The author reports the isolation and analysis of genomic clone of the mouse mafB gene. The gene lacks intron structure, at least, within its coding and 5'-untranslated sequences that are similar to the chicken mafB gene. RNA protection analysis determined one transcription initiation site of the gene at 389-bp upstream from the translation initiation site. Sequence analysis showed that the 5'-flanking region upstream to the ATG codon did not contain a conventional TATA box. A TATA-like sequence (5'-GATAAAA-3') and an inverted CCAAT-box (5'-ATTGG-3') were found to be located at nucleotide -31 and -86, referring to the transcription initiation site, respectively. Upstream to these sequences, there were several potential regulatory elements, including two GC-boxes (5'-GGGCGG-3': from -148 to -143; and from -123 to -118), and a palindromic sequence (5'-GTCAGCTGAC-3': from -164 to -155) which contained two halves-MARE (Maf recognition element), 5'-GCTGAC-3', and an E-box (5'-CAGCTG-3'). Promoter activity of the 5'-flanking region was analyzed by reporter transfection assay, which suggested that these segments were an important transcriptional activator. It was also suggested that MyoD transactivated the mouse mafB promoter and this gene was positively autoregulated by its product, MafB.
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PMID:Cloning and characterization of promoter of the mouse mafB gene. 1064 89

Maf oncoprotein is a basic-leucine zipper (bZip) type of transcriptional activator. Since many transcription factors are known to form functional complexes, we searched for proteins that interact with the DNA-binding domain of Maf using the phage display method and identified two homeodomain-containing proteins, Hoxd12 and MHox/Prx1/Phox1/Pmx1. Studies with mutants of Hox and Maf proteins showed that they associate through their DNA-binding domains; the homeodomain of Hox and the bZip domain of Maf, respectively. Reflecting the high similarity of the bZip domain, all other Maf family members tested (c-/v-Maf, MafB, MafK, MafF, and MafG) also associated with the Hox proteins. Pax6, whose homeodomain is relatively similar to MHox, also could interact with Maf. However, two other bZip oncoproteins, Fos and Jun, failed to associate with the Hox proteins, while a distantly related Hox family member, Meis1, could not interact with Maf. Through interactions with the bZip domain, the Hox proteins inhibited the DNA binding activity of Maf, whereas the binding of Hox proteins to their recognition sequences was not abrogated by Maf. We further showed that coexpression of the Hox proteins repressed transcriptional activation and transforming activity of Maf. These results suggested that the interaction of a set of Hox proteins with Maf family members may interfere not only with their oncogenicity but also with their physiological roles.
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PMID:A set of Hox proteins interact with the Maf oncoprotein to inhibit its DNA binding, transactivation, and transforming activities. 1103 80

The Maf oncoprotein is a basic leucine zipper (bZip)-bearing transcriptional activator that recognizes the Maf recognition element (MARE) DNA sequence. In this study, we investigated the role of Maf's transactivation function in cell transformation. Replacement of the conserved amino terminus transactivator domain of Maf by a heterologous and stronger transactivator domain (the acidic transactivator domain of VP16) resulted in enhanced transformation of chicken embryo fibroblast cells. In contrast, the fusing of a transcriptional repressor domain (Sin3 interaction domain of Mxi1) with the whole Maf protein masked the transactivator function of Maf, which in turn inhibited its transforming activity. Furthermore, the leucine zipper domain of Maf, which defines its dimer-forming specificity, was exchangeable with that of GCN4 yeast protein in terms of its transactivating and cell transforming activities. Thus, heterodimer formation with other bZip factors is not required for Maf's ability to transform. These results together suggest that transactivation through MARE is necessary for Maf-induced transformation and that there exist downstream target gene(s) for transformation. Since the MARE sequence overlaps with the recognition element of another bZip oncoprotein Jun, we assessed whether Jun and Maf induce cell transformation through activating the same genes. We thus constructed a mutated version of Jun that has a GCN4 leucine zipper and lacks the transactivator domain. This mutant repressed the cell transformation not only by Jun but also by Maf. Thus, Maf and Jun share downstream target gene(s) that are involved in cell transformation.
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PMID:Maf and Jun nuclear oncoproteins share downstream target genes for inducing cell transformation. 1146 1

Heme and its metabolism fulfill significant roles in many homeostatic and adaptative reactions. For example, heme (protein) senses oxygen concentration to regulate hypoxia response genes such as erythropoietin, and free heme, a proxidant, controls levels of several oxidative stress response proteins as well as that of a few enzymes in the heme metabolic pathway. Heme oxygenase (HO) is the key enzyme in heme catabolism, which degrades heme to Fe, CO, and biliverdin. CO is known as a gaseous messenger in the vascular and nervous systems. Biliverdin is rapidly converted to bilirubin, whose antioxidative effect is proposed to protect cells against reactive oxygen species. HO-1, the inducible isozyme of HO, is induced not only by its substrate heme, but also NO, metals, hypoxia, and various other stimuli. Studies on HO-1 deficiency indicate that induction of HO-1 is essential to homeostasis, at least in humans. Heme response elements (HREs), which mediate the induction of HO-1 expression by heme, are identified in enhancer regions of the mouse HO-1 gene. HRE shares a nucleotide sequence with the Maf recognition element (MARE). A transcriptional activator, Nrf2, has been shown to participate in HO-1 induction by several stimuli, including heme via HRE. A heme-binding transcription factor such as yeast Hap1 had been supposed to also exist in vertebrates, however, no such factor had been identified. Recently, we found that a mammalian transcription repressor, Bach1, directly binds heme, and that the DNA binding activity of Bach1 is negatively regulated by heme. Bach1 is capable of competing the binding to MARE with activators including Nrf2, therefore, HO-1 and other stress response genes bearing MARE may be regulated by heme via the MARE-binding transcription factors. Further analyses on the gene regulatory mechanism by heme would help us to understand the stress response system, especially against oxidative stress.
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PMID:[Heme metabolism in stress response]. 1186 90

The insulin gene is specifically expressed in beta-cells of the Langerhans islets of the pancreas, and its transcription is regulated by the circulating glucose level. Previous reports have shown that an unidentified beta-cell-specific nuclear factor binds to a conserved cis-regulatory element called RIPE3b and is critical for its glucose-regulated expression. Based on the sequence similarity of the RIPE3b element and the consensus binding sequence of the Maf family of basic leucine zipper transcription factors, we here identified mammalian homologue of avian MafA/L-Maf, an eye-specific member of the Maf family, as the RIPE3b-binding transcriptional activator. Reverse transcription-PCR analysis showed that mafA mRNA is detected only in the eyes and in pancreatic beta-cells and not in alpha-cells. MafA protein as well as its mRNA is up-regulated by glucose, consistent with the glucose-regulated binding of MafA to the RIPE3b element in beta-cell nuclear extracts. In transient luciferase assays, we also showed that expression of MafA greatly enhanced insulin promoter activity and that a dominant-negative form of MafA inhibited it. Therefore, MafA is a beta-cell-specific and glucose-regulated transcriptional activator for insulin gene expression and thus may be involved in the function and development of beta-cells as well as in the pathogenesis of diabetes.
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PMID:MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. 1236 92

Large Maf transcription factors, which are members of the basic leucine zipper (b-Zip) superfamily, have been reported to be involved in embryonic development and cell differentiation. Previously, we isolated a novel zebrafish large Maf cDNA, somite Maf1 (SMaf1), which possesses transactivational activity within its N-terminus domain. To elucidate SMaf1 function in mammals, we tried to isolate the mouse homologue of zebrafish SMaf1. We isolated the mouse homologue of zebrafish SMaf1, which is the same molecule as the recently reported MafA. MafA mRNA was detected in formed somites, head neural tube, and liver cells in the embryos. In the adult mouse, MafA transcript was amplified in the brain, lung, spleen, and kidney by RT-PCR. MafA mRNA was also detectable in beta-cell line. Next, we analyzed the transcriptional activity of MafA using rat insulin promoters I and II (RIPI and II), since a part of RIP sequence was similar to the Maf recognition element (MARE) and MafA was expressed in pancreatic beta cells. MafA was able to activate transcription from RIPII, but not RIPI, in a dose dependent manner and the activity was dependent on RIPE3b/C1 sequences. In addition, the amount of MafA protein was regulated by glucose concentration. These results indicate that MafA is the homologue of zebrafish SMaf1 and acts as a transcriptional activator of the insulin gene promoter through the RIPE3b element.
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PMID:Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter. 1468 Aug 41

Members of the Maf protooncogene and cap'n' collar families of basic-leucine zipper transcription factors play important roles in development, differentiation, oncogenesis, and stress signaling. In this study, we performed an in vivo protein-protein interaction screen to search for novel partners of the small Maf proteins. Using full-length human MAFG protein as bait, we identified the human basic-leucine zipper protein NRF3 [NF-E2 (nuclear factor erythroid 2)-related factor 3] as an interaction partner. Transfection studies confirmed that NRF3 is able to dimerize with MAFG. The resulting NRF3/MAFG heterodimer recognizes nuclear factor-erythroid 2/Maf recognition element-type DNA-binding motifs. Functional analysis revealed the presence of a strong transcriptional activation domain in the center region of the NRF3 protein. We found that NRF3 transcripts are present in placental chorionic villi from at least week 12 of gestation on through term. In particular, NRF3 is highly expressed in primary placental cytotrophoblasts, but not in placental fibroblasts. The human choriocarcinoma cell lines BeWo and JAR, derived from trophoblastic tumors of the placenta, also strongly express NRF3 transcripts. We generated a NRF3-specific antiserum and identified NRF3 protein in placental choriocarcinoma cells. Furthermore, we showed that NRF3 transcript and protein levels are induced by TNF-alpha in JAR cells. Our functional studies suggest that human NRF3 is a potent transcriptional activator. Finally, our expression and induction analyses hint at a possible role of Nrf3 in placental gene expression and development.
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PMID:Functional and placental expression analysis of the human NRF3 transcription factor. 1538 89


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