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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The highly leukemogenic avian retrovirus E26 expresses the two transcriptional activator-type oncogenes v-myb and v-ets as a nuclear fusion protein. Previous studies have shown that both oncogenes cooperate in the transformation of erythroid cells in vitro and that the phenotypes of transformed cells differ, depending on whether the oncogenes are coexpressed as separate proteins or as a fusion protein. Here we show that virus constructs encoding either v-Myb or v-Ets as their only oncoprotein are nonleukemogenic and that constructs coexpressing nonfused v-Myb and v-Ets proteins appear to be weakly leukemogenic. Surprisingly, leukemic animals injected with the latter contain highly leukemogenic variant viruses that exhibit internal deletions in their genome, resulting in the synthesis of novel Myb-Ets fusion proteins. These results show that v-Myb and v-Ets must be fused to cause leukemia and establish a new mechanism of oncogene activation and cooperation.
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PMID:Fusion of the nuclear oncoproteins v-Myb and v-Ets is required for the leukemogenicity of E26 virus. 207 Apr 21

The adenovirus E1A gene product is a potent transcriptional activator and nuclear oncoprotein. Like other regulatory proteins, E1A has a short half-life, in the range of 30 to 120 min. This short half-life, which was measured in cells synthesizing E1A, is not observed in cells injected with E1A protein made in bacteria or in vitro. In these cases, E1A is essentially refractory to degradation. In an attempt to reconcile this apparent paradox, we suggested that E1A was marked for degradation during its synthesis. Furthermore, we showed that a domain in the amino terminus of E1A was required for rapid degradation in cells translating E1A mRNA (J. M. Slavicek, N. C. Jones, and J. D. Richter, EMBO J. 7:3171-3180, 1988). In this study, we have used Xenopus laevis oocytes injected with mRNAs encoding altered E1A proteins to show that the amino-terminal tetrapeptide Met-Arg-His-Ile is required for E1A degradation. Even conservative amino acid substitutions in this degradation sequence render it nonfunctional. This degradation sequence can function as a transferable signal, since it induces instability when fused to another normally stable protein. Furthermore, the degradation sequence requires a proximity of no more than six residues from the amino terminus for activity. These data suggest that a trans-acting factor recognizes the amino terminus of E1A during the translation of its message to mark the protein for subsequent destruction.
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PMID:The degradation sequence of adenovirus E1A consists of the amino-terminal tetrapeptide Met-Arg-His-Ile. 214 91

In this report we study the effects of internal deletions of the yeast transcriptional activator HAP1 (CYP1) on activity at two dissimilar DNA binding sites, upstream activation sequence 1 (UAS1) of CYC1 (iso-1-cytochrome c) and CYC7 (iso-2-cytochrome c). These deletions remove up to 1061 amino acids of the 1483-residue protein and bring the carboxyl-terminal acidic activation domain closer to the amino-terminal DNA-binding domain. Surprisingly, the deletions have opposite effects at the two sites; activity at UAS1 increases with deletion size, while activity at CYC7 decreases. The mutant with the largest deletion, mini-HAP1, has no measurable activity at CYC7 but binds normally to the site in vitro. In contrast, a protein with the DNA-binding domain of HAP1 fused to the acidic activation domain of GAL4 is active at both UAS1 and CYC7. These findings are discussed in the context of two models that suggest how the DNA sequence can alter the activity of the bound HAP1. In a separate experiment, we generate a mutation in the DNA-binding domain of HAP1 that requires the addition of zinc for binding to either UAS1 or CYC7 in vitro. This finding shows that a zinc finger anchors DNA binding to both types of HAP1 sites.
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PMID:Internal deletions in the yeast transcriptional activator HAP1 have opposite effects at two sequence elements. 216 46

Transcription of the human neurotropic virus promoter, JCVE, and its regulation in glial cells are controlled by the 98 bp tandem repeats positioned between the viral early and late genes. Here, we show that a region, designated domain-D, located upstream from the 98 bp repeats functions as a transcriptional activator and increases JCVE promoter activity. Using the reporter SV40E promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, we demonstrate that domain-D stimulates the basal SV40E promoter activity in glial and to a lesser degree in HeLa cells. Results from gel mobility-shift assays indicate that domain-D interacts with proteins derived from glial and HeLa extracts and results in the formation of specific DNA-protein complexes. Through UV cross-linking assays, we demonstrate that these complexes have similar electrophoretic mobilities which comigrate with the 43-50 Kd proteins derived from glial and HeLa cells. These findings, together with our previous observations, imply that the JCVE control region is composed of multiple common and specific activator domains that may account for the increased expression of the promoter in glial cells. The possible role of the D-binding protein in transcription of the JCVE promoter is discussed.
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PMID:Regulation of a human neurotropic virus promoter, JCVE: identification of a novel activator domain located upstream from the 98 bp enhancer promoter region. 217 35

The OmpR binding sequence (OBS) in the upstream region of the ompF promoter of Escherichia coli was fused to 27 synthetic promoters. Transcription from a number of weak promoters, regardless of their sequences, was dramatically activated in the presence of OmpR, a transcriptional activator. In vivo DNA footprinting revealed that OmpR enhanced the binding of RNA polymerase to the promoters. This enhancement was essential for transcription of weak promoters, while OmpR binding to the OBS fused to a strong promoter was inhibitory for transcription. These results indicate that OmpR stabilizes the formation of an RNA polymerase-promoter complex, possibly a closed promoter complex, and that a transcription activator can serve not only as a positive but also as a negative regulator for gene expression.
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PMID:Enhancement of RNA polymerase binding to promoters by a transcriptional activator, OmpR, in Escherichia coli: its positive and negative effects on transcription. 219 74

Endothelin-1 (ET-1) is a 21-amino-acid peptide synthesized by endothelial cells that has potent vasoconstrictor activity. Human ET-1 is derived from a 212-amino-acid prepropeptide, termed preproendothelin-1 (PPET-1). To identify cis-acting sequences essential for PPET-1 gene transcription, bovine aortic endothelial (BAE) cells were transfected with plasmids containing 5'-flanking sequences of the human PPET-1 gene fused to the human growth hormone gene as a reporter. Deletional analysis of these fusion plasmids showed that the sequence spanning positions -141 to -127 of the human PPET-1 promoter is required for full transcription activity. Introduction of clustered point mutations into this region of the promoter reduced transcription activity. Gel shift analysis, methylation interference, protein-DNA cross-linking, and oligonucleotide competition studies revealed that BAE cell nuclear extract contains a 47-kilodalton DNA-binding protein recognizing the core motif TATC (GATA) located at positions -135 to -132 of the PPET-1 promoter. The size and specificity of this DNA-binding protein resemble GF-1, a previously described transcription factor of erythroid cells that binds to the same core motif. Gel shift analysis indicated that GF-1 and the DNA-binding protein interacting with the PPET-1 promoter have different tissue distributions; the former is restricted to a subset of hematopoietic cells, and the latter is found in various cell types, including BAE, NIH 3T3, and HeLa cells. By using an antiserum to the C-terminal region of GF-1, the two proteins were also found to be antigenically distinct. When a growth hormone fusion plasmid containing the proximal 141 nucleotides of the PPET-1 promoter was transfected into a variety of cell types, these was preferential expression in cells of endothelial origin. We conclude that a nuclear factor with binding specificity for a GATA motif similar to that of the transcriptional activator GF-1 is necessary for the efficient and cell-specific expression of the human PPET-1 gene.
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PMID:A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. 238 28

Cellular transcriptional activator sequences from a Syrian hamster cell line (baby hamster kidney (BHK] were rescued by a double selection procedure. An enhancer-deficient SV40 promoter was linked to the neomycin resistance (NEO) gene and transfected into BHK cells. Genomic DNA fragments of G418-resistant cell clones containing multiple copies of integrated plasmid DNAs were used for a second transfection of BHK cells, resulting in the genomic integration of a single copy plasmid which expresses the NEO gene efficiently. For rapid cloning of the integrated promoter and adjacent cellular DNA sequences, these cell clones were fused to COS-1 cells, thereby providing SV40 large T antigen and the monkey cell permissive factor necessary for SV40 replication. Resulting from this fusion, the integrated plasmid and adjacent sequences were amplified to about 1000 extrachromosomal copies giving rise to an abundant pool of promoter elements which thus can be cloned into a plasmid very easily for further investigations. Promoter analyses of three clones in the chloramphenicol acetyltransferase transient expression assay demonstrated that the recombination with cellular DNA enables the initially defective SV40 promoter to express at wild type levels.
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PMID:Rapid rescue of cellular transcriptional activator elements by amplification of a single copy selection gene. 254 5

Protein-protein interactions between two proteins have generally been studied using biochemical techniques such as crosslinking, co-immunoprecipitation and co-fractionation by chromatography. We have generated a novel genetic system to study these interactions by taking advantage of the properties of the GAL4 protein of the yeast Saccharomyces cerevisiae. This protein is a transcriptional activator required for the expression of genes encoding enzymes of galactose utilization. It consists of two separable and functionally essential domains: an N-terminal domain which binds to specific DNA sequences (UASG); and a C-terminal domain containing acidic regions, which is necessary to activate transcription. We have generated a system of two hybrid proteins containing parts of GAL4: the GAL4 DNA-binding domain fused to a protein 'X' and a GAL4 activating region fused to a protein 'Y'. If X and Y can form a protein-protein complex and reconstitute proximity of the GAL4 domains, transcription of a gene regulated by UASG occurs. We have tested this system using two yeast proteins that are known to interact--SNF1 and SNF4. High transcriptional activity is obtained only when both hybrids are present in a cell. This system may be applicable as a general method to identify proteins that interact with a known protein by the use of a simple galactose selection.
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PMID:A novel genetic system to detect protein-protein interactions. 254 63

The nucleotide sequence of the virG gene for a transcriptional activator on the agropine-type hairy-root-inducing plasmid pRiA4 was determined. The sequence contained one possible open reading frame. The gene product with a molecular size of 26.5 kDa was identified by an Escherichia coli coupled-transcription-translation system using cloned virG plasmids as templates. However, neither an ATG nor a GTG start codon which could give rise to such a protein was identified in the nucleotide sequence. Instead, TTG was found as a candidate for the start codon. This TTG was preceded, like most other TTG start codons, by both a Shine-Dalgarno (SD) sequence and a T signal which are respectively complementary to the 3'-end region of 16S rRNA and the T psi loop of initiator tRNA. Further evidence for the start at TTG was obtained by gene fusion experiments. When the E. coli lacZ gene, whose expression entirely depends on the transcription and translation from upstream regions, was connected in-phase with virG either directly upstream or downstream of the TTG sequence, only the latter fused gene expressed the beta-galactosidase activity in Agrobacterium cells in response to a plant phenolic compound, acetosyringone. The TTG codon preceded by an SD sequence and a T signal is also conserved in the virG sequences from other three tumor-inducing plasmids previously reported.
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PMID:Putative start codon TTG for the regulatory protein VirG of the hairy-root-inducing plasmid pRiA4. 267 Jun 79

OmpR and EnvZ, the protein products of the ompB locus, are regulatory components required for osmoexpression of outer membrane porin proteins, OmpF and OmpC, in Escherichia coli. EnvZ is considered to be an osmosensor which transmits signals across the membrane to OmpR, a transcriptional activator for ompF and ompC. We inserted the envZ gene into a high expression vector, pIN-III. Following cellular fractionation, EnvZ was found to be localized in the inner membrane. Sequence analysis revealed that the signal peptide-like N-terminal sequence was not removed from the purified EnvZ. A genetic approach using EnvZ/beta-lactamase fusion proteins was taken to determine the topology of EnvZ in the inner membrane. When beta-lactamase was fused after the N-terminal signal peptide-like sequence, ampicillin resistance, conferred by the beta-lactamase moiety of the fusion protein, was expressed. However, when beta-lactamase was fused after the second downstream apolar sequence, the cells showed very poor ampicillin resistance indicating that the enzyme was localized on the cytoplasmic side of the inner membrane. The results of this approach reveal that the hydrophilic region of EnvZ between the two apolar sequences is periplasmically localized and that the hydrophilic region downstream of the second apolar sequence is cytoplasmically directed. These results were confirmed by partial proteolysis of the fusion proteins in intact cells.
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PMID:Localization and membrane topology of EnvZ, a protein involved in osmoregulation of OmpF and OmpC in Escherichia coli. 282 92


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