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)

A cAMP response element (CRE) plays an important role in the cAMP-mediated gene regulation. Several factors that recognize a CRE have been characterized, and it has been shown that they need either covalent modification by protein kinase A or a cofactor such as the adenovirus Ela to function as an activator. In this study we show that the substance P precursor gene expression is regulated by protein kinase A and identify the CRE sequence in its promoter region. We find that a novel factor and ATF2 bind to the region containing the CRE of the substance P precursor gene. The sequence analysis indicates that the novel protein, designated CELF, has a significant homology to C/EBP gene family proteins in the carboxyl-terminal part containing the basic region and the leucine zipper motif. Ubiquitous expression of CELF suggests that this factor is utilized by various genes. Cell-free transcription analyses indicate that CELF is a constitutive transcriptional activator without apparent phosphorylation by protein kinase A. These results demonstrate that multiple factors are responsible for transcriptional control of the substance P precursor gene through the CRE region.
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PMID:Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor. 171 59

Using a DNA probe from the DNA-binding portion of the NF-IL6 gene and an antibody against the DNA-binding domain of NF-IL6, we isolated a gene homologous to NF-IL6 in the DNA-binding and leucine zipper domains. This intronless gene, termed NF-IL6 beta encodes a 269-amino acid protein with a potential leucine zipper structure, and the gene product can bind to the CCAAT homology as well as the viral enhancer core sequence, as in the cases of NF-IL6 and C/EBP. This gene is expressed at an undetectable or a minor level in normal tissues but is induced by lipopolysaccharide or inflammatory cytokines, as in the case of NF-IL6. NF-IL6 beta easily forms a heterodimer with NF-IL6 in vitro and the heterodimeric complex binds to the same DNA sequence as the respective homodimers. When examined by transient luciferase assays, NF-IL6 beta is consistently a stronger transactivator than NF-IL6. Furthermore, NF-IL6 beta shows a synergistic transcriptional effect with NF-IL6. These data suggest that NF-IL6 beta is an important transcriptional activator in addition to NF-IL6 in regulation of the genes involved in the immune and inflammatory responses.
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PMID:A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. 174 2

The rat aldolase B 5' flanking region (nucleotides - 194 to +41) contains sufficient information for liver-specific expression. A detailed investigation of factors binding to the rat aldolase B 5' flanking region has allowed us to identify three distinct factors that filled different sites of this region (A, B, C). The liver-enriched C/EBP or related factors bind to box C, as demonstrated by the specific interaction with bacterially expressed C/EBP protein. Box B bearing the CCAAT sequence binds the ubiquitous factor NFY. Surprisingly, Box A is able to bind two liver enriched factors, namely HNF1 and HNF3. However, in the context of the intact promoter, as shown by footprinting competition experiments, HNF3 binds solely to this sequence. HNF3, but not HNF1 is a transcriptional activator as demonstrated in the in vitro transcription assay.
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PMID:Interplay of an original combination of factors: C/EBP, NFY, HNF3, and HNF1 in the rat aldolase B gene promoter. 195 74

A putative transcription factor, C/EBP, isolated from rat liver nuclei, has been shown to bind to at least two different sequence motifs: the CCAAT promoter domain and a core sequence [GTGG(T/A)(T/A)(T/A)G] common to many viral enhancers, including simian virus 40 and human hepatitis B virus. It has been proposed that C/EBP might function as a positive transcription factor by facilitating the communication between promoter and enhancer elements through its dual binding activities to DNA. Surprisingly, results from three different approaches suggest that C/EBP functions as a transcriptional repressor to hepatitis B virus and simian virus 40. Further investigation indicated that C/EBP can function as both a transcriptional activator and a repressor, depending on the reporter gene system.
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PMID:Transcriptional activation and repression by cellular DNA-binding protein C/EBP. 215 40

The product of the c-myc proto-oncogene is a nuclear phosphoprotein whose normal cellular function has not yet been defined. c-Myc has a number of biochemical properties, however, that suggest that it may function as a potential regulator of gene transcription. Specifically, it is a nuclear DNA-binding protein with a short half-life, a high proline content, segments that are rich in glutamine and acidic residues, and a carboxyl-terminal oligomerization domain containing the leucine zipper and helix-loop-helix motifs that serve as oligomerization domains in known regulators of transcription, such as C/EBP, Jun, Fos, GCN4, MyoD, E12, and E47. In an effort to establish that c-Myc might regulate transcription in vivo, we sought to determine whether regions of the c-Myc protein could activate transcription in an in vitro system. We report here that fusion proteins in which segments of human c-Myc are linked to the DNA-binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene linked to GAL4-binding sites. Three independent activation regions are located between amino acids 1 and 143, a region that has been shown to be required for neoplastic transformation of primary rat embryo cells in cooperation with a mutated ras gene. These results demonstrate that domains of the c-Myc protein can function to regulate transcription in a model system and suggest that alterations of Myc transcriptional regulatory function may lead to neoplastic transformation.
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PMID:An amino-terminal c-myc domain required for neoplastic transformation activates transcription. 223 23

The full-length cDNA for a transcriptional activator, DBP, that binds to the D site of the albumin promoter has been cloned. DBP belongs to a family of related transcription factors including Fos, Jun, CREB, and C/EBP, which share a conserved basic domain. However, unlike most other members of this family, DBP does not contain a "leucine zipper" structure. Among several rat tissues tested, significant levels of its protein are only observed in liver; yet, with the exception of testis, DBP mRNA is present in all of the examined tissues. DBP as well as its mRNA accumulate to significant levels only in adult animals. During chemically induced liver regeneration, DBP expression is rapidly down-regulated, suggesting that DBP may be involved in the proliferation control of hepatocytes. This cell growth-dependent expression of DBP, in contrast to its tissue specificity, appears to be controlled at the level of mRNA accumulation.
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PMID:DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. 204 17

A structural motif for DNA-binding proteins, the 'leucine zipper', has been proposed for the jun, fos and myc gene products, the yeast transcriptional activator GCN4, and the C/EBP enhancer-binding protein. These proteins all contain a region with four or five leucine residues spaced exactly seven amino acid residues apart whose sequence is consistent with the formation of an amphipathic alpha-helix. It has been proposed that the leucine zipper consists of two interdigitated alpha-helices, one from each monomer, that constitute the dimerization function necessary for high-affinity binding to DNA; an adjacent region of basic residues is thought to be responsible for specific protein-DNA contacts. In support of this model, substitution of the leucine residues within the motif can abolish dimerization and DNA-binding, and a synthetic peptide corresponding to the GCN4 leucine zipper forms alpha-helical dimers. Despite the conserved leucine residues, however, each protein has a distinct dimerization specificity. Specifically, GCN4 homodimer, Jun homodimer and Fos-Jun heterodimer proteins bind to the same DNA site, whereas Fos is unable to form homodimers, bind DNA, or interact with GCN4 (refs 8-14). Here, we alter the dimerization specificity of Fos by precisely replacing its leucine zipper with that from GCN4. This Fos-GCN4 chimaeric protein is able to bind to the target site in the absence of Jun, and can form DNA-binding heterodimers with GCN4 but not with Jun. These results indicate that the leucine zipper is sufficient to confer dimerization specificity and strongly suggest that Fos contacts DNA directly.
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PMID:Changing fos oncoprotein to a jun-independent DNA binding protein with GCN4 dimerization specificity by swapping "leucine zippers". 250 87

The importance of C/EBP proteins in B cell biology is suggested by the occurrence of functionally important C/EBP binding sites in Ig gene enhancers and promoters, and the knowledge that family member NF-IL-6 is induced in other systems in response to regulators of B cell differentiation. We have studied the expression pattern and activity of C/EBP family transcriptional regulators in B cells at different developmental stages by using B cell lines and normal splenic B cells. Two family members, Ig/EBP and NF-IL-6, seem to be the major regulators of C/EBP site-dependent transcriptional activity in B cells. Negative regulator Ig/EBP is predominantly present in early B cells; activator NF-IL-6 increases in more mature B cells and is induced by LPS activation of splenic B cells. LIP, an N-terminally truncated form of NF-IL-6, was found in most B cell lines tested; LIP can act as a weak transcriptional activator in B cell lines. Partly as a result of the differential amounts of C/EBP family proteins, C/EBP sites do not function as activator sites in early B cells but are activator sites in terminally differentiated B cells.
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PMID:Limited expression of C/EBP family proteins during B lymphocyte development. Negative regulator Ig/EBP predominates early and activator NF-IL-6 is induced later. 796 64

The aromatic hydrocarbon (Ah) receptor complex is a ligand-activated transcriptional activator consisting of at least two protein components. The ligand-binding component is the AhR protein, a cytosolic receptor encoded by the Ahr gene, which, upon ligand binding, translocates to the nucleus in a heterodimeric complex with the ARNT (Ah receptor nuclear translocator) component. The complex binds to several discrete DNA domains containing aromatic hydrocarbon responsive elements (AhRE) present in the regulatory region of the murine cytochrome P(1)450 Cyp1a1 gene and of the other genes in the [Ah] gene battery. As a consequence of binding, a transcriptional complex is formed that activates the expression of these genes by as yet unidentified mechanisms. We have analyzed DNA-protein interactions in four of these domains, specifically, the AhREs located between -1085 and -482 (sites A, C, E, and D) of the upstream regulatory region of the murine Cyp1a1 gene. We found that two DNA-binding proteins, present in cytosolic and nuclear extracts of mouse Hepa-1 cells, showed overlapping DNA-binding specificities to those of the Ah receptor. One of these proteins had an apparent molecular mass of 35-40 kDa, bound only to AhRE3 (site D), and has been identified tentatively as a member of the C/EBP family of transcription factors. The second protein, purified by DNA-affinity chromatography, had an apparent molecular mass of 95 kDa and bound to a larger DNA motif that included the AhRE sequence, in AhRE3 and AhRE5 (sites D and A), but not in AhRE1 or AhRE2 (sites C and E). This protein was not AhR nor was it ARNT, since it was found in receptorless (Ahr-) and in nuclear translocation-defective (Arnt-) cells, as well as in cells that had not been exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), a potent inducer of Cyp1a1 expression. Evidence from in vivo methylation protection indicated that two G residues flanking AhRE3, one of which is required for binding of the 95-kDa protein, may be protected from methylation in uninduced cells and become exposed upon dioxin treatment, suggesting that the 95-kDa protein may be constitutively bound to AhRE3, and be displaced by binding of the Ah receptor complex. These results lend support to the concept that the transcriptional regulation of the [Ah] battery genes could be modulated by combinatorial interactions of the Ah receptor complex with other transcription factors.
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PMID:Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT). 798 Jun 46

The t(17;19) translocation in acute lymphoblastic leukemias results in creation of E2A-hepatic leukemia factor (HLF) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper (bZIP) protein HLF fused to a portion of E2A proteins with transcriptional activation properties. An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t(17;19)-bearing leukemias. All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3' with high affinity. Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline- and acidic amino acid-rich (PAR) and C/EBP subfamilies; however, E2A-HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site. These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A-HLF chimeras and were further exacerbated by a zipper mutation in one isolate. Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites. But on reporter genes with nonoptimal binding sites, their transcriptional properties diverged and E2A-HLF competitively inhibited activation by wild-type PAR proteins. These findings establish a spectrum of binding site-specific transcriptional properties for E2A-HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions.
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PMID:DNA-binding and transcriptional regulatory properties of hepatic leukemia factor (HLF) and the t(17;19) acute lymphoblastic leukemia chimera E2A-HLF. 806 31


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