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

In-frame codon insertion and deletion mutants were constructed in a plasmid containing the sequence that encodes ICP0, a transcriptional activator of herpes simplex virus type 1 (HSV-1). The effect of these mutations was analyzed in a transient expression assay using the promoters for, the IE-0 gene (an immediate early (alpha) gene), the thymidine kinase gene (an early (beta) gene), and the glycoprotein C gene (a late (gamma) gene) fused to reporter cassettes that encoded either beta-galactosidase or chloramphenicol acetyl transferase. Assays were performed in the presence or absence of a plasmid encoding ICP4, the major regulatory protein of HSV-1. Our results demonstrate that ICP0-mediated transactivation varied depending on the position of the insertion in the gene. One region of this protein was consistently shown to be required for full activation of each promoter examined either in the presence or in the absence of ICP4. This region overlaps with a cysteine-rich region and coincides with a transactivator domain identified in another extensive mutational analysis of this sequence. Analysis of the deletion mutants generated in this study demonstrated that the carboxy-terminal regions were required for activation in certain circumstances and that this varied depending on the promoter being assayed and the cell type in which the analysis was performed.
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PMID:Mutational analysis of the sequence encoding ICP0 from herpes simplex virus type 1. 184 23

The IE-0 gene of herpes simplex virus type 1 (HSV-1) contains two introns and encodes ICP0, a powerful transcriptional activator. We have isolated a cDNA clone that encodes ICP0 from a lambda gt10 cDNA library constructed from RNAs made from HSV-1-infected HeLa cells. DNA sequence analysis of this clone confirmed the predicted intron/exon boundaries (L. J. Perry, F. J. Rixon, R. D. Everett, M. C. Frame, and D. J. McGeoch, J. Gen. Virol. 67:2365-2380, 1986). Following transfection, a plasmid containing the cDNA copy of IE-0 directed the synthesis of ICP0, which was appropriately compartmentalized and distributed in the nucleus, as revealed by immunofluorescence. A transient expression assay was used to demonstrate that this cDNA copy retained the ability to transactivate the HSV-1 promoters for the IE-0 gene (an immediate-early gene), the thymidine kinase gene (an early gene), and the glycoprotein C gene (a late gene). The product of this cDNA clone cooperated with ICP4 to activate expression from the thymidine kinase gene promoter in a synergistic manner. The availability of a functional cDNA copy encoding ICP0 provides the opportunity to express this protein in vector systems that do not recognize eucaryotic donor and acceptor splicing signals to overexpress ICP0.
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PMID:Isolation and characterization of a functional cDNA encoding ICP0 from herpes simplex virus type 1. 184 9

We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed in cells bearing human T-cell leukemia virus type I (HTLV-I). HTLV-I has a trans-acting transcriptional activator, p40tax, that is thought to be implicated in leukemogenesis through the activation of cellular enhancers. With a subline (JPX-9) of the human T-cell line Jurkat, in which p40tax is inducible, gp34 was shown to be of cellular origin and to be transcriptionally activated by p40tax. It was also demonstrated that two species of mRNA are generated from one copy of the gp34 gene and that these mRNAs encode the identical gp34 product and differ in the 3' untranslated region. Analysis of the deduced amino acid sequence of gp34 showed that it lacks typical signal peptides; however, it has a hydrophobic stretch for membrane anchoring and four possible N-linked glycosylation sites at the carboxy-terminal portion, indicating that it belongs to the family of membrane proteins whose carboxy-terminal portion protrudes out of the cell. The gp34 gene displayed relatively delayed induction compared with other genes activated by p40tax. Taken together with the observation of the dependence of gp34 expression on HTLV-I p40tax, unlike other p40tax-dependent genes such as those for the interleukin-2 receptor alpha chain and c-fos, which are expressed or induced under physiological conditions, we predict that the mechanism involved in the induction of gp34 expression by p40tax is distinct from and more intricate than those for the previously characterized genes.
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PMID:Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. 199 93

Expression of the alpha-1 acid glycoprotein (AGP) gene (agp) is activated by a key transcription factor, AGP/enhancer-binding protein (AGP/EBP, commonly called C/EBP beta), in the liver during the acute-phase response. In addition to this positive regulation, agp is negatively regulated by nucleolin (T. H. Yang et al., Mol. Cell. Biol. 14:6068-6074, 1994). Other factors involve in positive regulation of the agp gene are poorly characterized. In a systematic search for factors that may interact with AGP/EBP, we have identified Nopp 140, a phosphoprotein of 140 kDa, by immunoaffinity chromatography. Nopp 140 not only functions as a transcriptional activator per se but also interacts with AGP/EBP to synergistically activate the agp gene in an AGP/EBP-binding motif-dependent manner. In addition to interacting with AGP/EBP, Nopp140 interacts specifically with TFIIB. Distinct regions of Nopp140 that interact with AGP/EBP and TFIIB have been characterized. The sequence of Nopp140 contains several stretches of serine- and acidic amino acid-rich sequences which are also found in ICP4 of herpes simplex virus type 1, a known transcription factor that interacts with TFIIB. The physical interaction between TFIIB and wild-type Nopp140 or several deletion mutants of Nopp140 correlates with the ability of Nopp140 to activate the agp gene synergistically with AGP/EBP. Thus, the molecular mechanism for agp gene activation may involve the interaction of AGP/EBP and TFIIB mediated by coactivator Nopp140.
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PMID:Identification and characterization of a nucleolar phosphoprotein, Nopp140, as a transcription factor. 897 3

An equine herpesvirus 1 (EHV-1) mutant was constructed by inserting a lacZ expression cassette into the intergenic region upstream of gene 62 (glycoprotein L; gL) and downstream of gene 63 (a homologue of the herpes simplex virus transcriptional activator ICP0). The recombinant lacZ62/63-EHV-1 had similar growth kinetics in cell culture to those of the parental wild type (wt) virus, with indistinguishable cytopathic effects and plaque morphology. Reverse transcriptase PCR confirmed that the lacZ insertion did not interfere with transcription of gL and immunoblot analysis indicated there was no modification to late gene expression as monitored by synthesis of EHV-1 glycoproteins C and D. The parental EHV-1 isolate HVS25A used here had almost identical nucleotide sequence to that published for isolate Ab4, in a 1200 bp region surrounding the insert, but lacked a HindIII site corresponding to Ab4 position 109,048. The lacZ62/63-EHV-1 caused respiratory disease in BALB/c mice with clinical signs, histopathology and virus titres in lungs throughout days 1-5 post infection similar to those induced by wt EHV-1. X-gal staining for beta-galactosidase expression in murine lungs clearly demonstrated EHV-1 infection in cells of the bronchiolar epithelium and pulmonary parenchyma, with a peak of infection evident at day 2 post infection, when up to 50% of bronchioles demonstrated blue-staining and thus virus-infected epithelial cells. The construction of this replication competent virus carrying a reporter gene identifies a site for insertion of foreign genes and will facilitate studies on the pathogenesis of EHV-1.
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PMID:An equine herpesvirus 1 mutant with a lacZ insertion between open reading frames 62 and 63 is replication competent and causes disease in the murine respiratory model. 985 3

Azospirillum represents the best characterized genus of plant growth-promoting rhizobacteria. Other free-living diazotrophs repeatedly detected in association with plant roots, include Acetobacter diazotrophicus, Herbaspirillum seropedicae, Azoarcus spp. and Azotobacter. Four aspects of the Azospirillum-plant root interaction are highlighted: natural habitat, plant root interaction, nitrogen fixation and biosynthesis of plant growth hormones. Each of these aspects is dealt with in a comparative way. Azospirilla are predominantly surface-colonizing bacteria, whereas A. diazotrophicus, H. seropedicae and Azoarcus sp. are endophytic diazotrophs. The attachment of Azospirillum cells to plant roots occurs in two steps. The polar flagellum, of which the flagellin was shown to be a glycoprotein, mediates the adsorption step. An as yet unidentified surface polysaccharide is believed to be essential in the subsequent anchoring phase. In Azoarcus sp. the attachment process is mediated by type IV pili. Nitrogen fixation structural genes (nif) are highly conserved among all nitrogen-fixing bacteria, and in all diazotrophic species of the class of proteobacteria examined, the transcriptional activator NifA is required for expression of other nif genes in response to two major environmental signals (oxygen and fixed N). However, the mechanisms involved in this control can vary in different organisms. In Azospirillum brasilense and H. seropedicae (alpha- and beta-subgroup, respectively), NifA is inactive in conditions of excess nitrogen. Activation of NifA upon removal of fixed N seems to involve, either directly or indirectly, the signal transduction protein P(II). The presence of four conserved cysteine residues in the NifA protein might be an indication that NifA is directly sensitive to oxygen. In Azotobacter vinelandii (gamma-subgroup) nifA is cotranscribed with a second gene nifL. The nifL gene product inactivates NifA in response to high oxygen tension and cellular nitrogen-status. NifL was found to be a redox-sensitive flavoprotein. The relief of NifL inhibition on NifA activity, in response to N-limitation, is suggested to involve a P(II)-like protein. Moreover, nitrogenase activity is regulated according to the intracellular nitrogen and O(2) level. In A. brasilense and Azospirillum lipoferum posttranslational control of nitrogenase, in response to ammonium and anaerobiosis, involves ADP-ribosylation of the nitrogenase iron protein, mediated by the enzymes DraT and DraG. At least three pathways for indole-3-acetic acid (IAA) biosynthesis in A. brasilense exist: two Trp-dependent (the indole-3-pyruvic acid and presumably the indole-3-acetamide pathway) and one Trp-independent pathway. The occurrence of an IAA biosynthetic pathway not using Trp (tryptophan) as precursor is highly unusual in bacteria. Nevertheless, the indole-3-pyruvate decarboxylase encoding ipdC gene is crucial in the overall IAA biosynthesis in Azospirillum. A number of genes essential for Trp production have been isolated in A. brasilense, including trpE(G) which codes for anthranilate synthase, the key enzyme in Trp biosynthesis. The relevance of each of these four aspects for plant growth promotion by Azospirillum is discussed.
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PMID:Azospirillum, a free-living nitrogen-fixing bacterium closely associated with grasses: genetic, biochemical and ecological aspects. 1097 48

ATF6 is a key transcriptional activator of the unfolded protein response (UPR), which allows mammalian cells to maintain cellular homeostasis when they are subjected to a variety of environmental and physiological stresses that target the endoplasmic reticulum (ER). ATF6, a 90-kDa ER transmembrane protein, contains three evolutionarily conserved N-linked glycosylation sites within its carboxyl luminal domain. Although it is well established that p90ATF6 activation requires transit from the ER to the Golgi, where it is cleaved by the S1P/S2P protease system to generate a nuclear form p60ATF6 that acts as a transcriptional activator, the functional significance of p90ATF6 N-linked glycosylation is unknown. Here we show that ER Ca(2+) depletion stress, a triggering mechanism for the UPR, induces the formation of ATF6(f), which represents de novo partial glycosylation of newly synthesized p90ATF6. By mutating a single amino acid within the N-linked glycosylation site closest to the carboxyl terminus of p90ATF6, we recreated ATF6(f). This mutation sharply reduces p90ATF6 association with calreticulin, a major Ca(2+)-binding chaperone for N-glycoprotein. We further determined that ATF6(f) exhibits a faster rate of constitutive transport to the Golgi, resulting in a higher level of p60ATF6 in the nucleus and stronger transactivating activity in the absence of ER stress. Additional analysis of p90ATF6 mutants targeting single or multiple N-glycosylation sites also showed higher constitutive transactivating activity than wild type ATF6. Because accumulation of underglycosylated proteins in the ER is a potent inducer for the UPR, these studies uncover a novel mechanism whereby the glycosylation status of p90ATF6 can serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the UPR.
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PMID:Underglycosylation of ATF6 as a novel sensing mechanism for activation of the unfolded protein response. 1469 59

Bovine herpesvirus 1 (BHV-1), like other Alphaherpesvirinae subfamily members, establishes latency in sensory neurons. The latency-related (LR) RNA is abundantly expressed during latency, and expression of an LR protein is required for the latency reactivation cycle in cattle. Within LR promoter sequences, a 135-amino-acid open reading frame (ORF) was identified, ORF-E, that is antisense to the LR RNA. ORF-E is also downstream of the gene encoding the major viral transcriptional activator, bICP0. Strand-specific reverse transcription-PCR demonstrated that a transcript containing ORF-E was consistently expressed in trigeminal ganglia (TG) of latently infected calves, productively infected cultured cells, and acutely infected calves. As expected, a late transcript encoding glycoprotein C was not detected in TG of latently infected calves. The ORF-E transcript is polyadenylated and is expressed early when cultured bovine cells are productively infected. Protein coding sequences containing ORF-E were fused to green fluorescent protein (GFP) to examine the cellular localization of the putative protein. In transiently transfected mouse neuroblastoma (neuro-2A) and human neuroblastoma (SK-N-SH) cells, the ORF-E/GFP fusion protein was detected in discreet domains within the nucleus. In contrast, the ORF-E/GFP fusion protein was detected in the cytoplasm and nucleus of rabbit skin cells and bovine kidney cells. As expected, the GFP protein was expressed in the cytoplasm and nucleus of transfected cells. These studies indicate that the ORF-E transcript is consistently expressed during latency. We suggest that the ORF-E gene regulates some aspect of the latency reactivation cycle.
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PMID:Identification of a novel bovine herpesvirus 1 transcript containing a small open reading frame that is expressed in trigeminal ganglia of latently infected cattle. 1511 22

The invasive and filamentous growth forms of Saccharomyces cerevisiae are adaptations to specific environmental conditions, under particular conditions of limited nutrient availability. Both growth forms are dependent on the expression of the FLO11 gene, which encodes a cell-wall-associated glycoprotein involved in cellular adhesion. A complex regulatory network consisting of signaling pathways and transcription factors has been associated with the regulation of FLO11. Mss11p has been identified as a transcriptional activator of this gene, and here we present an extensive genetic analysis to identify functional relationships between Mss11p and other FLO11 regulators. The data show that Mss11p is absolutely required for the activation of FLO11 by most proteins that have previously been shown to affect FLO11 expression, including the signaling proteins Ras2p, Kss1p, and Tpk2p, the activators Tec1p, Flo8p, and Phd1p, and the repressors Nrg1p, Nrg2p, Sok2p, and Sfl1p. The genetic evidence furthermore suggests that Mss11p activity is not dependent on the presence of any of the above-mentioned factors and that the protein also regulates other genes involved in cellular adhesion phenotypes. Taken together, the data strongly suggest a central role for Mss11p in the regulatory network controlling FLO11 expression, invasive growth, and pseudohyphal differentiation.
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PMID:Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. 1546 24

Here, we describe the construction of a set of binary adenovirus vectors encoding for a tetracycline-regulatable expression cassette and the Tet-ON or the Tet-OFF transcriptional activator proteins from a single viral chromosome. The rabies virus glycoprotein was cloned into the E1 region and the tetracycline activator proteins were inserted in both orientation in place of the E3 region. To further restrict background transcription, we also introduced a Lac repressor protein based roadblock to transcription elongation. To make the system more versatile it has been engineered into the commonly used AdEasy system. We show that rabies virus glycoprotein expression is tightly regulated with an essentially undetectable basal expression and a several 100-fold induced expression. In our vector backbone, the Tet-ON and the Tet-OFF systems appears to work with essentially the same efficiency. Thus, the choice of principle can be based on whether a positive or negative regulation of reporter gene activity is desirable. Taken together our results suggest that the binary vectors described here should be a valuable addition to the repertoire of viral vectors used in basic and medical research.
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PMID:Binary AdEasy vector systems designed for Tet-ON or Tet-OFF regulated control of transgene expression. 1610 68


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