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

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) consists of W1W2 repeats and a unique C-terminal Y1Y2 domain and plays a critical role in EBV-induced transformation. To identify the cellular proteins associating with EBNA-LP, we performed a yeast two-hybrid screen using EBNA-LP cDNA containing a single W1W2 domain as bait and an EBV-transformed human peripheral blood lymphocyte cDNA library as the source of cellular genes. Our results were as follows. (i) A cDNA in the positive yeast colony was found to encode a cellular protein, human oestrogen-related receptor 1 (hERR1), which is a constitutive transcriptional activator of the various types of oestrogen response elements. (ii) A purified chimeric protein consisting of glutathione S-transferase (GST) fused to hERR1 specifically formed complexes with EBNA-LPs containing one (EBNA-LPR1), two (EBNA-LPR2) or four W1W2 repeats (EBNA-LPR4) transiently expressed in COS-7 cells. Reciprocally, GST fused to EBNA-LPR1 or EBNA-LPR2 pulled down hERR1 transiently expressed in COS-7 cells. (iii) Mutational analyses of EBNA-LP revealed that the Y2 domain of EBNA-LP is responsible for the interaction with hERR1 and two leucines in the Y2 domain (Leu-78 and -82), which are conserved among a subset of primate gammaherpesviruses, are interactive sites for hERR1. So far, it has been reported that the only domain of EBNA-LP critical for EBV-induced transformation is the Y1Y2 domain. Potential roles of hERR1 in EBV-induced transformation are discussed.
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PMID:Physical interaction of Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) with human oestrogen-related receptor 1 (hERR1): hERR1 interacts with a conserved domain of EBNA-LP that is critical for EBV-induced B-cell immortalization. 1256 May 63

The HTLV-1 transcriptional activator Tax is required for viral replication and pathogenesis. In concert with human CREB, Tax recruits the human transcriptional coactivator and histone acetyltransferase p300/CBP to the HTLV-1 promoter. Here we investigate the structural features of the interaction between Tax and the KIX domain of p300/CBP. Circular dichroism spectroscopy, nuclear magnetic resonance chemical shift perturbation mapping, and sedimentation equilibrium analysis show that KIX binds a Tax subdomain corresponding to residues 59-98 of Tax (called Tax(59-98)). Circular dichroism spectroscopy suggests that Tax(59-98) is intrinsically disordered (natively unfolded) in isolation and adopts an ordered conformation upon binding KIX. The interaction is disrupted by a single amino acid variation of Tax(59-98) in which leucine 68 is substituted with proline. Chemical shift perturbation mapping reveals that the Tax-binding surface of KIX is distinct from that utilized by CREB, and corresponds to the site of KIX that interacts with the human transcription factors c-Jun and mixed lineage leukemia protein (MLL). Sedimentation equilibrium analysis shows that Tax and the phosphorylated KID domain of CREB can simultaneously bind KIX to form a ternary 1:1:1 complex. The results provide a molecular description of the concerted recruitment of p300/CBP via the KIX domain by Tax and phosphorylated CREB during Tax-mediated gene expression.
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PMID:KIX-mediated assembly of the CBP-CREB-HTLV-1 tax coactivator-activator complex. 1458 Jan 93

OsGRF1 (Oryza sativa GROWTH-REGULATING FACTOR1) is a rice gene encoding a putative novel transcriptional regulator. We identified and characterized eleven homologs of OsGRF1 in the rice genome. All twelve OsGRF proteins have two highly conserved regions, the QLQ (Gln, Leu, Gln) and WRC (Trp, Arg, Cys) domains, and sequences reminiscent of transcription factors. OsGRF genes were preferentially expressed in young and growing tissues, and applied gibberellic acid (GA3) enhanced the expression of seven OsGRF genes. In situ hybridization showed high levels of OsGRF1 transcripts in the shoot apical meristem and in cells surrounding the vasculature of the intercalary meristem. In a GAL4-based yeast assay, the C-terminal region of OsGRF1 was found to have transactivation activity. These results indicate that OsGRF1 acts as a transcriptional activator. Based on the in situ expression pattern of OsGRF1, we postulate that it may be involved in regulating vegetative growth in rice.
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PMID:Whole genome analysis of the OsGRF gene family encoding plant-specific putative transcription activators in rice (Oryza sativa L.). 1529 73

REPRESSION OF SHOOT GROWTH (RSG) is a tobacco (Nicotiana tabacum) transcriptional activator with a basic Leu zipper domain that regulates endogenous amounts of gibberellins (GAs) by the control of a GA biosynthetic enzyme. The 14-3-3 signaling proteins have been suggested to suppress RSG by sequestering it in the cytoplasm. Here, we show that RSG phosphorylation on Ser-114 is important for 14-3-3 binding. We found that GA levels regulate the intracellular localization of RSG. RSG translocated into the nucleus in response to a reduction in GA levels. GA treatment could reverse this nuclear accumulation. The GA-induced disappearance of RSG-green fluorescent protein from the nucleus did not depend on protein degradation. By contrast, the mutant RSG (S114A) that could not bind to 14-3-3 continued to be localized predominantly in the nucleus after GA application. Analysis of the mRNA levels of GA biosynthetic genes showed that the feedback regulation of the GA 20-oxidase gene was inhibited in transgenic plants expressing a dominant negative form of RSG. Our results suggest that RSG is negatively modulated by GAs by 14-3-3 binding and might be involved in GA homeostasis.
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PMID:Involvement of 14-3-3 signaling protein binding in the functional regulation of the transcriptional activator REPRESSION OF SHOOT GROWTH by gibberellins. 1537 59

As in many other Gram-negative phytopathogenic bacteria, the Hrp type III secretion system is essential for the pathogenicity of Ralstonia solanacearum on host plants. The expression of most of the type III effector genes previously isolated from R. solanacearum is co-regulated with those of hrp genes by an AraC-type transcriptional activator, HrpB. In order to isolate type III-related pathogenicity genes, we screened hrpB-regulated genes in R. solanacearum. Using a transposon-based system, we isolated 30 novel hpx (hrpB-dependent expression) genes outside the hrp gene cluster. Most of the hpx genes contain a PIP (plant-inducible promoter) box-like motif in their putative promoter regions. Seven hpx genes encoded homologues of known type III effectors and type III-related proteins found in other animal and plant pathogens. Four encoded known enzymes, namely, glyoxalase I, Nudix hydrolase, spermidine synthase and transposase. Interestingly, six hpx genes encoded two types of leucine-rich repeat (LRR) protein. Products of the remaining genes did not show any significant homology to known proteins. We also identified two novel hrpB-regulated genes, hpaZ and hpaB, downstream of hrpY in the hrp cluster. The hpaB gene of R. solanacearum, but not hpaZ, was required for both the pathogenicity and ability to induce hypersensitive reaction on plants. We show that a hpaB null mutant still produces Hrp pili on the cell surface although it shows a typical Hrp-defective phenotype on plants.
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PMID:Genetic screening of Hrp type III-related pathogenicity genes controlled by the HrpB transcriptional activator in Ralstonia solanacearum. 1552 73

Saccharomyces cerevisiae senses extracellular amino acids using two members of the family of amino acid transporters, Gap1 or Ssy1; aspects of the latter are reviewed here. Despite resemblance with bona fide transporters, Ssy1 appears unable to facilitate transport. Exposure of yeast to amino acids results in Ssy1-dependent transcriptional induction of several genes, in particular some encoding amino acid transporters. Amino acids differ strongly in their potency, leucine being the most potent one known. Using a selection system in which potassium uptake was made dependent on amino acid signalling, our laboratory has obtained and described gain-of-function mutations in SSY1. Some alleles conferred inducer-independent signalling; others increased apparent affinity for inducers. These results revealed that amino acid transport is not required for signalling and support the notion that sensing by Ssy1 occurs via its direct interaction with extracellular amino acids. Current work includes development of quantitative assays of sensing. We use the finding by Per Ljungdahl's laboratory that the signal transduction from Ssy1 involves proteolytic removal of an inhibitory part of the transcriptional activator Stp1. Protein-A Z-domain fused to the C-terminus of Stp1 and Western analysis using antibody against horseradish peroxidase allow quantification of sensing.
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PMID:Amino acid sensing by Ssy1. 1566 21

Salmonella enterica serovar Typhimurium is lysogenized by several temperate bacteriophages that encode lysogenic conversion genes, which can act as virulence factors during infection and contribute to the genetic diversity and pathogenic potential of the lysogen. We have investigated the temperate bacteriophage called Gifsy-1 in S.enterica serovar Typhimurium and show here that the product of the gogB gene encoded within this phage shares similarity with proteins from other Gram-negative pathogens. The amino-terminal portion of GogB shares similarity with leucine-rich repeat-containing virulence-associated proteins from other Gram-negative pathogens, whereas the carboxyl-terminal portion of GogB shares similarity with uncharacterized proteins in other pathogens. We show that GogB is secreted by both type III secretion systems encoded in Salmonella Pathogenicity Island-1 (SPI-1) and SPI-2 but translocation into host cells is a SPI-2-mediated process. Once translocated, GogB localizes to the cytoplasm of infected host cells. The genetic regulation of gogB in Salmonella is influenced by the transcriptional activator, SsrB, under SPI-2-inducing conditions, but the modular nature of the gogB gene allows for autonomous expression and type III secretion following horizontal gene transfer into a heterologous pathogen. These data define the first autonomously expressed lysogenic conversion gene within Gifsy-1 that acts as a modular and promiscuous type III-secreted substrate of the infection process.
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PMID:Genetic and molecular analysis of GogB, a phage-encoded type III-secreted substrate in Salmonella enterica serovar typhimurium with autonomous expression from its associated phage. 1584 15

We have identified four mutations in Xenopus TFIIIA that increase the stability of TFIIIA-5 S rRNA gene complexes. In each case, the mutation has a relatively modest effect on equilibrium binding affinity. In three cases, these equilibrium binding effects can be ascribed primarily to decreases in the rate constant for protein-DNA complex dissociation. In the fourth case, however, a substitution of phenylalanine for the wild-type leucine at position 148 in TFIIIA results in much larger compensating changes in the kinetics of complex assembly and dissociation. The data support a model in which a relatively unstable population of complexes with multi-component dissociation kinetics forms rapidly; complexes then undergo a slow conformational change that results in very stable, kinetically homogeneous TFIIIA-DNA complexes. The L148F mutant protein acts as a particularly potent transcriptional activator when it is fused to the VP16 activation domain and expressed in yeast cells. Substitution of L148 to tyrosine or tryptophan produces an equally strong transcriptional activator. Substitution to histidine results in genetic and biochemical effects that are more modest than, but similar to, those observed with the L148F mutation. We propose that an amino acid with a planar side chain at position 148 can intercalate between adjacent base pairs in the intermediate element of the 5 S rRNA gene. Intercalation occurs slowly but results in a very stable DNA-protein complex. These results suggest that transcriptional activation by a cis-acting sequence element is largely dependent on the kinetic, rather than the thermodynamic, stability of the complex formed with an activator protein. Thus, transcriptional activation is dependent in large part on the lifetime of the activator-DNA complex rather than on binding site occupancy at steady state. Introduction of intercalating amino acids into zinc finger proteins may be a useful tool for producing artificial transcription factors with particularly high in vivo activity.
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PMID:Mutations in TFIIIA that increase stability of the TFIIIA-5 S rRNA gene complex: unusual effects on the kinetics of complex assembly and dissociation. 1588 46

The protein Sac7d belongs to a class of small chromosomal proteins from the hyperthermophilic archaeon Sulfolobus acidocaldarius. Sac7d is extremely stable to heat, acid, and chemical agents. This protein is a monomer and it binds DNA without any particular sequence preference, while inducing a sharp kink in the DNA. By appending a leucine-zipper-like helical peptide derived from the yeast transcriptional activator GCN4 to the C-terminal end of Sac7d, the modified monomers (denoted S7dLZ) are expected to interact with each other via hydrophobic force to form a parallel dimer. The recombinant S7dLZ was expressed in Escherichia coli and purified by heating and ion-exchange chromatography. The formation of dimer was detected by gel-filtration chromatography and chemical cross-link. The results of surface plasmon resonance and circular dichroism experiments showed that the DNA-binding capacity was retained. Furthermore, X-ray diffraction analysis of single crystals of S7dLZ in complex with DNA decamer CCTATATAGG showed that the leucine-zipper segments of S7dLZ were associated into an antiparallel four-helix bundle. There are two DNA fragments bound to each S7dLZ tetramer in the crystal. This model works as a successful template that endows protein a new function without losing original properties.
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PMID:Design and characterization of a multimeric DNA binding protein using Sac7d and GCN4 as templates. 1602 19

The traJ gene of the virulence plasmid of Salmonella enterica serovar Typhimurium (pSLT) encodes a transcriptional activator of the transfer operon. The leucine-responsive regulatory protein (Lrp) is an activator of traJ transcription. The upstream-activating-sequence of the pSLT traJ promoter contains two Lrp binding sites (LRP-1 and LRP-2), both necessary for transcriptional activation. The promoter-proximal site (LRP-2) contains a GATC site (GATC-II) whose methylation state affects Lrp binding: GATC-II methylation in both DNA strands decreases the affinity of Lrp for the LRP-2 site, while efficient Lrp binding occurs to a non-methylated GATC-II site. The effect of GATC-II hemimethylation on Lrp binding is strand-specific: methylation of the traJ non-coding strand permits formation of the major Lrp-DNA retardation complex, but methylation of the coding strand does not. This asymmetry supports a model in which passage of the replication fork may permit Lrp-mediated activation of conjugal transfer in one daughter plasmid molecule but not in the other. A remarkable trait of this regulatory design is that hemimethylation of a single GATC site can generate distinct epigenetic signals in otherwise identical plasmid DNA molecules.
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PMID:Regulation of traJ transcription in the Salmonella virulence plasmid by strand-specific DNA adenine hemimethylation. 1613 35


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