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

Tumor suppressor protein p53 is a potent transcriptional activator and regulates cell growth negatively. To characterize the transcriptional activation domain (TAD) of p53, various point mutants were constructed in the context of Gal4 DNA binding domain and tested for their transactivation ability. Our results demonstrated that the positionally conserved hydrophobic residues shared with herpes simplex virus VP16 and other transactivators are essential for transactivation. Also, the negatively charged residues and proline residues are necessary for full activity, but not essential for the activity of p53 TAD. Deletion analyses showed that p53 TAD can be divided into two subdomains, amino acids 1-40 and 43-73. An in vitro glutathione S-transferase pull-down assay establishes a linear correlation between p53 TAD-mediated transactivation in vivo and the binding activity of p53 TAD to TATA-binding protein (TBP) in vitro. Mutations that diminish the transactivation ability of Gal4-p53 TAD also impair the binding activity to TBP severely. Our results suggest that at least TBP is a direct target for p53 TAD and that the binding strength of TAD to TBP (TFIID) is an important parameter controlling activity of p53 TAD. In addition, circular dichroism spectroscopy has shown that p53 TAD peptide lacks any regular secondary structure in solution and that there is no significant difference between the spectra of the wild type TAD and that of the transactivation deficient mutant type.
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PMID:Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein. 755 31

Infection of cells with herpes simplex virus type 1 (HSV-1) results in a rapid alteration of phosphorylation on the large subunit of cellular RNA polymerase II (RNAP II), most likely on its C-terminal domain (S. A. Rice, M. C. Long, V. Lam, C. A. Spencer, J. Virol. 68:988-1001, 1994). This phosphorylation modification generates a novel form of the large subunit which we have designed IIi. In this study, we examine roles that HSV-1 gene products play in this process. An HSV-1 mutant defective in the immediate-early transcriptional activator protein ICP4 is able to efficiently induce IIi. Viruses having mutations in the genes for the ICP0, ICP6, or ICP27 proteins are also competent for IIi formation. In contrast, 22/n199, an HSV-1 mutant which contains a nonsense mutation in the gene encoding the immediate-early protein ICP22, is significantly deficient in IIi induction. This effect is seen in Vero cells, where 22/n199 grows relatively efficiently, and in human embryonic lung (HEL) cells, where 22/n199 growth in more restricted. RNAP II is recruited into viral replication compartments in 22/n199-infected cells, indicating that altered phosphorylation of RNAP II is not a prerequisite for nuclear relocalization of RNAP II. In addition, we show by nuclear run-on transcription analysis that viral gene transcription is deficient in HEL cells infected with 22/n199. Viral late gene transcription does not occur efficiently, and antisense transcription throughout the genome is diminished compared with that of the wild-type HSV-1 infection. These transcriptional effects cannot be explained by differences in viral DNA replication, since 22/n199 replicates its DNA efficiently in HEL cells. Our results demonstrated that ICP22 is necessary for virus-induced aberrant phosphorylation of RNAP II and for normal patterns of viral gene transcription in certain cell lines.
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PMID:Herpes simplex virus immediate-early protein ICP22 is required for viral modification of host RNA polymerase II and establishment of the normal viral transcription program. 763

The ZEBRA protein has a unique biological function among herpesviral proteins. It is responsible for the disruption of Epstein-Barr virus (EBV) latency and the induction of the lytic cycle. ZEBRA is a bZIP transcriptional activator which binds as a dimer to 7-bp response elements within EBV promoters and is directly involved in the stimulation of virus replication at the EBV lytic origin. We have employed the ZEBRA/EBV biological system to test whether a heterologous activation domain can substitute for another activation domain (the ZEBRA domain). The ZEBRA activation region was replaced with the potent acid activation region from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein. Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself. Activation was not target- or cell-type dependent, nor was it dependent on the presence of virus. These activation domains restored ZEBRA's ability to induce early antigen and to stimulate origin replication to levels that were equal to or greater than those of wild type. These studies suggest that the specificities of some of the known biological functions of ZEBRA are not dependent upon the nature of the activation domain present within ZEBRA.
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PMID:Restoration of the Epstein-Barr virus ZEBRA protein's capacity to disrupt latency by the addition of heterologous activation regions. 764 37

The herpes simplex virus transactivator VP16 directs the assembly of a multicomponent protein-DNA complex with cellular components Oct-1 and VCAF-1, contributing a potent carboxyl-terminal acidic activation domain that is essential for activation of gene expression in mammalian cells. We show here that VP16, devoid of this acidic activation domain, functions as a strong transcriptional activator in the yeast Saccharomyces cerevisiae when appended onto a heterologous GAL4 DNA binding domain, as determined by measuring activation of a resident GAL1:lacZ reporter gene. Deletion analysis indicated that sequences contained within the amino-terminal 369 amino acids of VP16 were necessary for transactivation by truncated VP16. Activation by truncated VP16 in yeast was comparable to that observed with a hybrid protein consisting of the GAL4 DNA binding domain linked to the VP16 acidic activation domain. Similar GAL4-VP16 hybrid proteins were only marginally active in mammalian cells. Sequence requirements for transactivation by truncated VP16 can be demarcated from domains of VP16 that are required for interaction with VCAF-1 and for protein-DNA complex formation with Oct-1. Our findings indicate that VP16 contains additional sequences upstream of the acidic activation domain that may play a direct role in transactivation.
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PMID:Transcriptional activation by DNA-binding derivatives of HSV-1 VP16 that lack the carboxyl-terminal acidic activation domain. 774 69

Interferon consensus sequence binding protein (ICSBP) is a member of the interferon regulatory factor (IRF) family of proteins that include IRF-1, IRF-2, and ISGF3gamma which share sequence similarity at the putative DNA binding domain (DBD). ICSBP is expressed exclusively in cells of the immune system and acts as a repressor of interferon consensus sequence (ICS) containing promoters that can be alleviated by interferons. In this communication, we have searched for functional domains of ICSBP by dissecting the DBD from the repression activity. The putative DBD of ICSBP (amino acids 1-121) when fused in frame to the transcriptional activation domain of the herpes simplex VP16 (ICSBP-VP16) is a very strong activator of ICS-containing promoters. In addition, ICSBP-VP16 fusion construct transfected into adenovirus (Ad) 12 transformed cells enabled cell surface expression of major histocompatibility complex class I antigens as did treatment with interferon. On the other hand, the DBD of the yeast transcriptional activator GAL4 was fused in frame to a truncated ICSBP in which the DBD was impaired resulting in a chimeric construct GAL4-ICSBP. This construct is capable of repressing promoters containing GAL4 binding sites. Thus, ICSBP contains at least two independent domains: a DBD and a transcriptional repressor domain. Furthermore, we have tested possible interactions between ICSBP and IRFs. The chimeric construct GAL4-ICSBP inhibited the stimulated effect of IRF-1 on a reporter gene, implying for a possible interaction between IRF-1 and ICSBP. Electromobility shift assays, demonstrated that ICSBP can associate with IRF-2 or IRF-1 in vitro as well as in vivo. Thus, ICSBP contains a third functional domain that enables the association with IRFs. These associations are probably important for the fine balance between positive and negative regulators involved in the interferon-mediated signal transduction pathways in cells of the immune system.
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PMID:Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. 776

Infected-cell polypeptide 4 (ICP4) of herpes simplex virus is both a transcriptional activator and a repressor. It has been previously demonstrated that both SP1-activated transcription and USF-activated transcription are repressed by ICP4 without affecting basal transcription (B. Gu, R. Rivera-Gonzalez, C. A. Smith, and N. A. DeLuca, Proc. Natl. Acad. Sci. USA 90:9528-9532, 1993; R. Rivera-Gonzalez, A. N. Imbalzano, B. Gu, and N.A. DeLuca, Virology 202:550-564, 1994). In this study, it was found that ICP4 repressed the activation function of two other activators, VP16 and ICP4 itself, in vitro. ICP4 inhibited transcription by interfering with the formation of transcription initiation complexes without affecting transcription elongation. Repression of activator function required that an ICP4 DNA binding site was present in one orientation within approximately 45 bp 3' to the TATA box. DNA binding by ICP4 was necessary but not sufficient for repression. ICP4 has been shown to form tripartite complexes cooperatively with the TATA box-binding protein and TFIIB on DNA containing an ICP4 binding site and a TATA box (C. A. Smith, P. Bates, R. Rivera-Gonzalez, B. Gu, and N. DeLuca, J. Virol. 67:4676-4687, 1993). A region of ICP4 that enables the molecule to form tripartite complexes was also required in addition to the DNA binding domain for efficient repression. Moreover, repression was observed only when the ICP4 binding site was in a position that resulted in the formation of tripartite complexes. Together, the data suggest that ICP4 represses transcription by binding to DNA in a precise way so that it may interact with the basal transcription complex and inhibit some general step involved in the function of activators. The steps or interactions involved in transcriptional activation that are inhibited by ICP4 are discussed.
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PMID:Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. 779 69

Eukaryotic transcriptional activators have been classified on the basis of the characteristics of their activation domains. Acidic activation domains, such as those in the yeast GAL4 or GNC4 proteins and the herpes simplex virus activator VP16, stimulate RNA polymerase II transcription when introduced into a variety of eukaryotic cells. This species interchangeability demonstrates that the mechanism by which acidic activation domains function is highly conserved in the eukaryotic kingdom. To determine whether such a conservation of function exists for a different class of activation domain, we have tested whether the glutamine-rich activation domains of the human transcriptional activator Sp1 function in the yeast Saccharomyces cerevisiae. We report here that the glutamine-rich domains of Sp1 do not stimulate transcription in S. cerevisiae, even when accompanied by human TATA-box binding protein (TBP) or human-yeast TATA-box binding protein hybrids. Thus, in contrast to the case for acidic activation domains, the mechanism by which glutamine-rich domains stimulate transcription is not conserved between S. cerevisiae and humans.
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PMID:The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces cerevisiae. 782 62

Infected-cell protein 4 (ICP4) is the major transcriptional activator of herpes simplex virus (HSV) gene expression during productive infection. ICP0 has broad transactivating activity for all classes of HSV genes as well as cellular genes and genes of heterologous viruses. Together, the transactivating activities of ICP4 and ICP0 are synergistic. ICP27, which alone does not exhibit major transregulatory activity, is able to differentially activate and repress viral gene expression induced by ICP4 and ICP0. Thus, ICP27 plays a modulatory role in viral gene expression. In order to explore the functional relationships among ICP4, ICP0, and ICP27 in the regulation of viral gene expression, we have used indirect immunofluorescence to examine the intracellular localization of ICP4 in cells infected with wild-type virus or with mutant viruses that did not express functional forms of ICP0 or ICP27. Although ICP4 localized to both the nuclei and cytoplasm of cells infected with either the wild-type virus or an ICP0 null mutant virus, this protein was present exclusively in the nuclei of cells infected with an ICP27 null mutant virus, suggesting that ICP27 is able to inhibit the nuclear localization of ICP4 during virus infection. Transient expression assays with pairs of plasmids that express wild-type forms of ICP4 and ICP0 or of ICP4 and ICP27 demonstrated that ICP27 has a significant inhibitory effect on the nuclear localization of ICP4, confirming the observations made with the mutant-virus-infected cells. By using a plasmid expressing wild-type ICP4 and a series of ICP27 mutant plasmids in transient expression assays, the C-terminal half of ICP27 was shown to be required for its inhibitory effect on the nuclear localization of ICP4. In similar studies using a series of ICP4 mutant plasmids, the region of ICP4 responsive to wild-type ICP27 was mapped to the C-terminal portion of the molecule between amino acid residues 820 and 1029. The level of expression of ICP27 was shown to have a significant effect on the intracellular localization of ICP4 in transient assays. These findings are consistent with previous studies in which ICP27 was shown to have an inhibitory effect on the nuclear localization of ICP0 (Z. Zhu, W. Cai, and P. A. Schaffer J. Virol. 68:3027-3040, 1994). Thus, ICP27 has a significant inhibitory effect on the ability of the two major HSV type 1 (HSV-1) regulatory proteins to localize to the nucleus. Collectively, these findings indicate that cooperative regulation of HSV-1 gene expression may well involve intracellular compartmental constraints.
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PMID:Intracellular localization of the herpes simplex virus type 1 major transcriptional regulatory protein, ICP4, is affected by ICP27. 798 45

The chimeric transcriptional activator tTA, a fusion between the Tn10 encoded Tet repressor and the activation domain of the Herpes simplex virion protein VP16, was stably expressed in transgenic tobacco plants. It stimulates transcription of the beta-glucuronidase (gus) gene from an artificial promoter consisting of 7 tet operators and a TATA-box. Tetracycline, which interferes with binding of tTA to operator DNA, reduces gus expression over several orders of magnitude. This stringency of regulation suggests that the system can be used to construct transgenic plants encoding a potentially lethal gene product. Furthermore, the specific and fast inactivation of tTA allows study of the stability of RNAs and proteins.
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PMID:A chimeric transactivator allows tetracycline-responsive gene expression in whole plants. 801 6

The equine herpesvirus type 1 (EHV-1) immediate-early (IE) gene product, an ICP4 homolog, is the major regulatory protein encoded by EHV-1 during cytolytic infection. The IE gene product has been demonstrated to induce reporter gene expression directed by both homologous and heterologous viral promoters, including the EHV-1 thymidine kinase (tk) promoter, the herpes simplex virus type 1 (HSV-1) tk and ICP4 promoters, and the simian virus 40 early promoter. In this report, the transcriptional activation domain of the EHV-1 IE gene product was mapped to within an acidic, 87-amino-acid region (amino acids 3 to 89) at the amino-terminus of the IE molecule. It is demonstrated that the IE transcriptional activation domain, when fused to the DNA-binding domain of the yeast transcriptional activator GAL4, can activate gene expression in cell lines derived from at least two different species. Moreover, it is shown that the EHV-1 IR2 gene product (Harty and O'Callaghan, J. Virol. 65, 3829-3838, 1991), a truncated form of the IE polypeptide lacking IE amino acid residues 1-322 (and, therefore lacks the deduced transcriptional activation domain), fails to transactivate the EHV-1 tk promoter, but retains the ability to down-regulate the EHV-1 IE promoter. Fusion of the acidic transcriptional activation domain of the HSV-1 virion protein VP16 to the transactivation-deficient IR2 gene product restored the ability of this truncated IE polypeptide to transactivate the EHV-1 tk promoter. These findings suggest a role for the IR2 protein as a trans-repressor of EHV-1 gene expression.
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PMID:The equine herpesvirus type 1 immediate-early gene product contains an acidic transcriptional activation domain. 803 Feb 39


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