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

Plasmids containing the varicella zoster virus (VZV) open reading frames (ORFs) 61 and 62 were used in a transient co-transfection assay to test for trans-activation of the VZV and herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) promoters. The trans-activating potential of the polypeptides encoded by these VZV ORFs, designated p51 and p140, was compared to that of their HSV-1 homologs ICP0 and ICP4, respectively. VZV p51 was functionally inactive in this system while p140 appeared to be a much stronger transcriptional activator than ICP4. Co-transfection of plasmids encoding VZV p140 and HSV-1 ICP0 resulted in a synergistic activation of the reporter gene as has been shown for the combination of ICP4 and ICP0.
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PMID:Trans-activation of viral tk promoters by proteins encoded by varicella zoster virus open reading frames 61 and 62. 215 90

A novel mammalian regulatory system was created by using the Escherichia coli lac repressor. The lac repressor was converted into a mammalian transcriptional activator by modifying the lac repressor coding region to include a nuclear localization signal from the simian virus 40 (SV40) large tumor antigen and the transcription activation domain from the herpes simplex virus type 1 virion protein 16. The lac activator protein (LAP) fusions were potent activators of several promoters containing lac operator sequences positioned either upstream or downstream of the transcription unit. A single lac operator allowed for transactivation, whereas multiple operators acted synergistically when separated by a small distance. Promoters containing 14 or 21 operator sequences were induced at least 1,000-fold in response to LAP, reaching levels of activity 20 to 30 times greater than that of the SV40 early promoter in HeLa cells. Activation was strongly inhibited by isopropyl-beta-D-thiogalactoside (IPTG), indicating that LAP retained the functions needed for allosteric regulation. LAP was bifunctional, also acting as a repressor of expression of an SV40 promoter containing an operator immediately downstream of the TATA box. Finally, genetic selection schemes were developed such that LAP-expressing cell lines can be generated at high frequency from either established or primary cells in culture.
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PMID:Conversion of the lac repressor into an allosterically regulated transcriptional activator for mammalian cells. 216 73

We have compared the transcriptional efficiencies of a number of eukaryotic promoters following DNA-mediated transfection into cultured rat hepatoma cells. We find that the highest levels of expression for the bacterial chloramphenicol acetyltransferase (CAT) reporter gene are observed with a herpes simplex virus type 1 (HSV-1) immediate early promoter when co-transfected with an expression construct bearing the gene for the HSV-1 transcriptional activator protein VP16. This transactivation phenomenon is specific for the HSV-1 immediate early promoter and increases the expression of the reporter gene 7-fold. Expression from the ICP4 promoter is 2.5-fold greater than the other promoters tested. In addition, expression from the ICP4 promoter can be induced, at varying times following transfection, by infecting the cells with HSV-1 viral particles. Two plasmids have been constructed which contain the HSV-1 ICP4 promoter adjacent to a multiple cloning site. One of the plasmids also contains SV40 splicing and polyadenylation signals.
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PMID:High efficiency transient expression of eukaryotic genes: use of an HSV-1 immediate early promoter (ICP4). 216 63

Varicella-zoster (VZV) gene 62 encodes a protein with a predicted Mr of 140,000 (140K) which has considerable amino acid identity with the major immediate early (IE) protein Vmw175 (ICP4) of herpes simplex virus type I (HSV-1). Vmw175 is an essential virus polypeptide with a pivotal role in the activation of early and late viral gene expression and also in the repression of IE gene expression. The VZV 140K protein has been shown to function as a strong transcriptional activator in transfection assays and largely complements for the loss of Vmw175 function in HSV-1. We report the results of cotransfection experiments which demonstrate that the 140K protein strongly represses expression from its own promoter, that of gene 62, thus establishing further functional similarity between it and Vmw175. However, whereas Vmw175 can substitute for the 140K protein in repression of the gene 62 promoter, the 140K protein does not repress the HSV-1 IE3 promoter in the reciprocal experiment. The integrity of a domain of Vmw175 (designated region 2), previously shown to be crucial for repression of the HSV-1 IE3 promoter, is also required for repression of the gene 62 promoter. Moreover, a similar requirement for the highly similar region 2 of the 140K protein for repression is demonstrated, suggesting that VZV 140K protein and HSV-1 Vmw175 autoregulate IE gene expression by a related mechanism.
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PMID:The product of varicella-zoster virus gene 62 autoregulates its own promoter. 217 91

The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV-mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV-infected cells for the therapy of HIV-mediated pathogenesis.
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PMID:Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. 224 44

Infection of human epidermoid carcinoma No. 2 cells with herpes simplex virus type 1 (HSV-1) leads to a reorganization of antigens associated with both the small and heterogeneous nuclear ribonucleoprotein complexes (snRNP and hnRNP). The hnRNP core protein antigens remain associated with the host chromatin, which appears to collapse into internal aggregates and along the nuclear envelope. More striking is the formation of prominent clusters of snRNP antigens (both general and U1 snRNP specific), which appear to condense throughout the nucleus then migrate to the periphery. These snRNP clusters have been identified at the fine structure level by immuno-electron microscopy. The HSV-1 presumed transcriptional activator ICP4, DNA-binding protein ICP8, and two capsid proteins ICP5 and p40 are not detectably associated with the snRNP clusters. Similar reorganization of snRNP occurs with HSV-2 and upon infection of African green monkey VERO cells with HSV-1. We speculate that the snRNP clusters arise from an increase in size and density of the interchromatin granule region of the host cell as a result of the partial inactivation of snRNP and host pre-mRNA splicing.
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PMID:Redistribution of nuclear ribonucleoprotein antigens during herpes simplex virus infection. 282 25

We report the complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1, as 6633 base pairs of composition 79.5% G+C. This contains immediate early gene 3, encoding the IE175 protein, an important transcriptional activator of later virus genes. The IE175 coding region was identified as a 3894 base sequence of 81.5% G+C DNA. The base composition of this gene is thus the most extreme yet determined, and the IE175 predicted amino acid composition is correspondingly biased, most notably with an alanine content of 20.9%. Functionally important regions of the IE175 polypeptide were tentatively identified by comparison with the sequence of the homologous protein from varicella-zoster virus and from locations of ts mutations, and were correlated with properties of the amino acid sequence. Aspects of the evolution of such an extreme composition DNA sequence were discussed.
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PMID:Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. 300 80

The nuclear localization of the herpes simplex virus transcriptional activator protein ICP4 was studied by indirect immunofluorescence. At early times after viral infection, ICP4 quickly localized to a diffuse intranuclear distribution. ICP4 later concentrated in globular compartments within the nucleus. The redistribution to the compartments was dependent on viral DNA replication. Double staining for ICP4 and ICP8, the early major DNA-binding protein, revealed that both were found in the same intranuclear globular compartments at late times. These were previously named "replication compartments" (M. P. Quinlan, L. B. Chen, and D. M. Knipe, Cell 36:857-868, 1984). Because ICP4 and ICP8 are known to function in transcriptional activation and DNA replication, respectively, both DNA replication and late transcription may occur in these compartments. The association of ICP4 and ICP8 with the replication compartments appeared to be independent in that the retention of ICP8 in the compartments required ongoing viral DNA synthesis, while the association of ICP4 was independent of viral DNA synthesis once the compartments were formed. Because ICP4 shows a different distribution at early and late times, stimulation of transcription by ICP4 may involve different molecular events or contacts during these two periods of the replicative cycle.
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PMID:Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4. 302 60

The immediate-early promoters of herpes simplex virus give rise to the first series of transcripts after infection. These promoters are composed of compound sequence elements that govern basal level and regulated transcription. The response of three core (truncated) promoters from the herpes simplex virus type 1 IE-4, IE-0, and IE-27 genes to a battery of virus-encoded trans-acting proteins was examined in a short-term transient expression assay system. The results of this study reveal (i) a role for a sequence, 5'---GGGGG---3', flanked by 3 to 5 base pairs of symmetry (the G box), which is present in the upstream region of all immediate-early gene promoters, (ii) a requirement for the consensus sequence protected by ICP4 for autoregulation by this immediate-early gene product, and (iii) an alternative, sequence-independent mechanism for the augmentation of alpha gene expression by the virion-associated transcriptional activator Vmw65, now designated as TIF.
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PMID:Dissection of immediate-early gene promoters from herpes simplex virus: sequences that respond to the virus transcriptional activators. 304 Oct 38

Mutations in Vp1 and ABl3 genes of maize and Arabidopsis lead to drastic reductions in the synthesis of a subset of maturation-specific products including seed storage proteins. Gene Phaseolus vulgaris ABl3-like factor (PvAlf), whose protein product is similar to the ABl3 and Vp1 proteins, has been cloned. Here, it is shown that PvAlf positively regulates phaseolin and phytohemagglutinin (PHA-L) promoters in particle bombardment assays. PvAlf mRNA expression is embryo-specific and temporally complex. PvAlf mRNA abundance is highest during two periods (9-14 and 22-35 days after flowering) that precede the onsets of seed maturation and seed abscission, respectively. Protein fusions with the DNA-binding domain of the yeast transcriptional activator GAL4 demonstrated that the N-terminal 243 amino acids of PvAlf function as a strong transcriptional activation domain in yeast (Saccharomyces cerevisiae) and plant cells. This domain consists of a central cluster rich in serine, threonine and proline (STP cluster) flanked by two negatively charged regions containing bulky hydrophobic residues similar to acidic activation domains of Vp1, the herpes simplex virus virion protein VP16 and transcription factors GCN4 and HAP4 from yeast. Together with the Vp1 proteins of maize and rice and ABl3, PvAlf constitutes a class (Vp1/ABl3-like factors or VAlfs) of regulatory factors that are pivotal for the promotion of seed maturation and dormancy in angiosperms.
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PMID:PvAlf, an embryo-specific acidic transcriptional activator enhances gene expression from phaseolin and phytohemagglutinin promoters. 755 Mar 72


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