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

Epstein-Barr virus (EBV) nuclear protein 2 (EBNA-2) is essential for EBV-induced B-cell transformation in vitro. EBNA-2 contains a 14-amino acid domain that directly activates transcription and is required for transformation. To determine whether another transcriptional activator can substitute for this function, a chimeric virus was constructed that contained a portion of the transcriptional activation domain from the herpes simplex virus VP16 protein inserted in place of the 14-amino acid domain of EBNA-2. The chimeric virus was able to transform B cells efficiently and transactivate expression of EBV and B-cell genes. Randomization of the 14-amino acid sequence in the domain markedly reduced its transcriptional activating activity and the transforming efficiency of the recombinant EBV. Mutation of a tryptophan within the 14-amino acid domain of EBNA-2 completely abolished transcriptional activation and B-cell transformation. These experiments indicate that EBNA-2 and VP16 activate transcription by similar mechanisms and that transcriptional activation is required for EBV-induced B-cell transformation.
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PMID:A region of herpes simplex virus VP16 can substitute for a transforming domain of Epstein-Barr virus nuclear protein 2. 132 41

We have previously shown that the human immunodeficiency virus type 1 (HIV-1) Tat protein can activate a synthetic promoter containing consensus-binding sites for the cellular transcription factor Sp1. In this report, we show that a GAL-Tat fusion protein targeted via GAL4 DNA-binding sites can also trans activate an HIV-1 LTR promoter independently of the trans-activation response region. To show that the trans activation of the promoter by Tat directly involves the Sp1 protein, we have targeted a GAL-Sp1 fusion protein to the long terminal repeat promoter via upstream GAL4-binding sites. In the presence of Tat and GAL-Sp1, the promoter is synergistically trans activated at the transcriptional level, indicating that Tat and Sp1 functionally interact to trans activate the HIV-1 promoter. The Sp1 synergism is relatively specific, since another chimeric transcriptional activator, GAL-VP16, does not appear to be significantly synergistic with Tat.
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PMID:Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1. 158 36

The human spumaretrovirus (HSRV) genome contains, in addition to coding information for the structural proteins, open reading frames (ORFs) for at least three additional genes termed bel1, bel2 and bel3. We report here the localization of the transcriptional activator of HSRV to the bel1 ORF. In reporter-based transient expression assays in COS cells utilizing the bacterial CAT gene linked to HSRV LTR sequences between -710 and +309 with respect to the transcriptional initiation site, co-expression of the bel1 gene product alone caused an over 100 to 300-fold increase in the level of LTR activity. High-level trans-activation by bel1 was specific for the HSRV LTR, as relatively minor positive and negative regulatory effects were observed on HIV-1 LTR and RSV LTR expression, respectively, whereas HTLV-1 LTR activity remained unaffected. Distinct regions of the HSRV LTR were found to be involved in bel1-induced trans-activation. Specifically, deletions between -500 and -389 and between -136 and -62 in the U3 region resulted in a 4- and 30 to 35-fold decline, respectively, in the response to bel1. Limited mutagenesis of the bel1 ORF indicated that most of the bel1 coding region, except for the carboxy-terminal 27 residues, is essential for the activation function.
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PMID:Distinct cis-acting regions in U3 regulate trans-activation of the human spumaretrovirus long terminal repeat by the viral bel1 gene product. 164 56

This review focuses on the gene-enzyme relationships and the regulation of different levels of the aromatic amino acid biosynthetic pathway in a simple eukaryotic system, the unicellular yeast Saccharomyces cerevisiae. Most reactions of this branched pathway are common to all organisms which are able to synthesize tryptophan, phenylalanine, and tyrosine. The current knowledge about the two main control mechanisms of the yeast aromatic amino acid biosynthesis is reviewed. (i) At the transcriptional level, most structural genes are regulated by the transcriptional activator GCN4, the regulator of the general amino acid control network, which couples transcriptional derepression to amino acid starvation of numerous structural genes in multiple amino acid biosynthetic pathways. (ii) At the enzyme level, the carbon flow is controlled mainly by modulating the enzyme activities at the first step of the pathway and at the branch points by feedback action of the three aromatic amino acid end products. Implications of these findings for the relationship of S. cerevisiae to prokaryotic as well as to higher eukaryotic organisms and for general regulatory mechanisms occurring in a living cell such as initiation of transcription, enzyme regulation, and the regulation of a metabolic branch point are discussed.
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PMID:Aromatic amino acid biosynthesis in the yeast Saccharomyces cerevisiae: a model system for the regulation of a eukaryotic biosynthetic pathway. 194 92

The transcriptional activator LAC9, a GAL4 homolog of Kluyveromyces lactis which mediates lactose and galactose-dependent activation of genes involved in the utilization of these sugars can also confer glucose repression to those genes. Here we report on the isolation and characterization of LAC9-2, an allele which encodes a glucose-sensitive activator in contrast to the one previously cloned. A single amino acid exchange of leu-104 to tryptophan is responsible for the glucose-insensitive phenotype. The mutation is located within the Zn-finger-like DNA binding domain which is highly conserved between LAC9 and GAL4. Glucose repression is also eliminated by duplication of the LAC9-2 allele. The data indicate that LAC9 is a limiting factor for beta-galactosidase gene expression under all growth conditions and that glucose reduces the activity of the activator.
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PMID:A mutation in the Zn-finger of the GAL4 homolog LAC9 results in glucose repression of its target genes. 210 31

The LEU3 protein of yeast activates a number of genes in the branched chained amino acid pathways. Native LEU3 is modulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis. alpha-Isopropylmalate is needed for transcriptional activation, but not for DNA binding. We show here that the transcriptional activation function of LEU3 resides within the C-terminal 32 amino acids. An adjacent stretch of 81 residues is dispensable and apparently forms a connecting link between the activation domain and a large central region previously identified as important for modulation. The newly defined activation domain contains a cluster of three tryptophan residues, each of which was changed to alanine by site-directed mutagenesis. Surprisingly, all three Trp----Ala mutations affect modulation. One of them, Trp-864----Ala, creates a LEU3 molecule that is largely unmodulated and also is a better transcriptional activator than is wild type LEU3 ("hyperactivator"). The other two mutations (Trp-861----Ala and Trp-870----Ala) change the modulation ratio but have no effect on the maximal activation efficiency of the activator. We propose that the activation domain of LEU3 is kept silent by association with the central region of the protein and that an alpha-isopropylmalate-induced conformational change in the central region releases and thus activates the activation domain.
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PMID:Transcriptional activator LEU3 of yeast. Mapping of the transcriptional activation function and significance of activation domain tryptophans. 221 32

Human lymphotropic virus, HTLV-1, encodes in its proviral genome a transcriptional activator protein, tax-1, that may be responsible for the development of virus-induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin-2 (IL-2) and one of its receptor (IL-2R) components, the IL-2 receptor alpha-chain (IL-2R alpha). In the present study, an expression plasmid containing tax-1 cDNA under the control of HTLV-1 LTR was introduced into mouse and human CD4-positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL-2R alpha; (ii) the IL-2R alpha expression was not permanent, as the IL-2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL-2R alpha expression in the transformants is due to a cell-cycle-regulated expression and function of tax-1. Furthermore, a proportion of the induced IL-2R in EL-4 was in high-affinity form, suggesting the association of the IL-2R alpha and the IL-2R beta chain (p70-75) components.
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PMID:Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR-linked tax-1 gene. 279 77

Rous sarcoma virus expresses a transcriptional activator that affects the LTR as well as other promoters. We discern this activity as a stimulation of the transient expression of an LTR-promoted hybrid transcriptional unit and also of the rat preproinsulin II gene in transfected NIH 3T3 cells. We map the activity to an alternate reading frame in the p19-p10 region of the gag gene and identify a mRNA whose spliced structure would direct translation of this reading frame from the Pr76gag initiation codon. This mRNA probably differs from genomic RNA only by the 282 nucleotide splice. The predicted translation product is a 124 residue polypeptide; the first six amino acids arise from gag. The target for the action of this transcriptional modulator at the LTR lies between 111 and 620 nucleotides upstream of the cap site.
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PMID:Rous sarcoma virus encodes a transcriptional activator. 298 97

Human T-cell leukemia virus type I has a unique sequence pX and the product p40x was proposed to be a specific trans-acting transcriptional activator of expression of the viral gene. Recently, a second pX protein p27x-III in addition to p40x was identified; these two proteins are encoded by overlapping frames III and IV (x-lor). For determination of which product is the trans-acting activator, site-directed mutations were introduced into the pX sequence which was placed under the metallothionein promoter. On cotransfection with pLTR-CAT (a plasmid containing the LTR of HTLV-I and chloramphenicol acetyltransferase gene), only the mutations that affected p40x expression inactivated the transcriptional activation from the LTR.
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PMID:The p40x of human T-cell leukemia virus type I is a trans-acting activator of viral gene transcription. 300 3

The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-kappa B.
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PMID:The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines. 750 13


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