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)

Nitrogen regulation of transcription in Escherichia coli requires sensation of the intracellular nitrogen status and control of the dephosphorylation of the transcriptional activator NRI-P. This dephosphorylation is catalyzed by the bifunctional kinase/phosphatase NRII in the presence of the dissociable PII protein. The ability of PII to stimulate the phosphatase activity of NRII is regulated by a signal transducing uridylyltransferase/uridylyl-removing enzyme (UTase/UR), which converts PII to PII-UMP under conditions of nitrogen starvation; this modification prevents PII from stimulating the dephosphorylation of NRI approximately P. We used purified components to examine the binding of small molecules to PII, the effect of small molecules on the stimulation of the NRII phosphatase activity by PII, the retention of PII on immobilized NRII, and the regulation of the uridylylation of PII by the UTase/UR enzyme. Our results indicate that PII is activated upon binding ATP and either 2-ketoglutarate or glutamate, and that the liganded form of PII binds much better to immobilized NRII. We also demonstrate that the concentration of glutamine required to inhibit the uridylyltransferase activity is independent of the concentration of 2-ketoglutarate present. We hypothesize that nitrogen sensation in E. coli involves the separate measurement of glutamine by the UTase/UR protein and 2-ketoglutarate by the PII protein.
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PMID:The Escherichia coli PII signal transduction protein is activated upon binding 2-ketoglutarate and ATP. 762 80

The homeodomain is a DNA-binding domain present in a large family of eukaryotic regulatory proteins. Homeodomain proteins have been shown to play key roles in controlling developmental programs in various organisms. Here we report the isolation and characterisation of a homeobox gene from Arabidopsis thaliana designated ATK1. The gene was isolated using as a probe the homeobox domain of the KN1 gene from maize. The homeodomain of ATK1 is highly homologous to the homeodomain of the KN1 gene of maize (81%) but shows only poor homology outside the homeodomain. Therefore ATK1 is probably not the Arabidopsis homologue of the KN1 gene from maize. It contains the four invariant amino acid residues present in the recognition helix 3 of all other homeodomain proteins. Outside the homeodomain a region rich in aspartate and glutamate residues is found suggesting that ATK1 is a transcriptional activator. The gene contains four introns which is similar in the KN1 gene of maize and the Osh1 gene of rice. Primer extension reveals the presence of two transcription initiation sites. The leader sequence of the genuine transcript is 342 nucleotides long and contains two upstream open reading frames. ATK1 is strongly expressed in the shoot apex of seedlings, while in mature plants the gene is primarily expressed in flowers and inflorescence stems. Such an expression pattern is reminiscent of that of the KN1 gene of maize and therefore ATK1 could similarly be involved in determining cell fate.
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PMID:The homeobox gene ATK1 of Arabidopsis thaliana is expressed in the shoot apex of the seedling and in flowers and inflorescence stems of mature plants. 764 3

Bacteriophage T4 middle promoters, which are transcribed using phage-modified host RNA polymerase and the T4 transcriptional activator, MotA, match the host sigma 70 consensus sequence at -10, but they have a different consensus ((t/a)(t/a)TGCTT(t/c)A) (a MotA box) at -30. While the T4 middle promoter PuvsX has these -10 and -30 motifs, it also has matches to the MotA box at -35, -51, -70, and -87. We show that MotA binds to PuvsX DNA, footprinting a region that includes the MotA boxes at -30, -35, and -51. Very high levels of MotA are required for footprinting and gel-shift experiments, and protein-DNA complexes formed in the presence of both phage-modified polymerase and MotA are more resistant to HindIII cleavage than those formed with either protein alone. These results suggest that MotA-DNA interactions may be stabilized by phage-modified polymerase. Sequences between -18 and -38 are absolutely required for MotA activation of transcription, but sequences upstream of -38 are stimulatory, particularly when chloride instead of glutamate is the major anion. Our results dissect PuvsX into a core promoter, downstream of -38, which is required for MotA activation, and an upstream region that enhances transcription especially under conditions less favourable for protein-DNA interactions.
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PMID:The bacteriophage T4 middle promoter PuvsX: analysis of regions important for binding of the T4 transcriptional activator MotA and for activation of transcription. 778 37

The divergently transcribed nasA gene and nasB operon are required for nitrate and nitrite assimilation in Bacillus subtilis. The beta-galactosidase activity of transcriptional lacZ fusions from the nasA and nasB promoters was high when cells were grown in minimal glucose medium containing poor nitrogen sources such as nitrate, proline, or glutamate. The expression was very low when ammonium or glutamine was used as the sole nitrogen source. The repression of the genes during growth on good sources of nitrogen required wild-type glutamine synthetase (GlnA), but not GlnR, the repressor of the glnRA operon. Primer extension analysis showed that the -10 region of each promoter resembles those of sigma A-recognized promoters. Between the divergently oriented nasA and nasB promoters is a region of dyad symmetry. Mutational analysis led to the conclusion that this sequence is required in cis for the activation of both nasA and nasB. The derepression of these genes in a glnA mutant also required this sequence. These results suggest that an unidentified transcriptional activator and glutamine synthetase function in the regulation of nasA and the nasB operon.
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PMID:Nitrogen regulation of nasA and the nasB operon, which encode genes required for nitrate assimilation in Bacillus subtilis. 783 89

The yeast CIT1 (mitochondrial citrate synthase) gene is subject to glucose repression and is further repressed by glucose plus glutamate. Based on deletion analysis of a CIT1-lacZ gene fusion, DNA sequences between -548 and -273 are required for full expression of CIT1. The region of transcription initiation and the putative TATA element are located at -150 to -100 and -195 respectively. A restriction fragment containing DNA sequences between -457 and -211 conferred activation and glucose-glutamate regulation when placed in either orientation upstream of a UAS-less heterologous yeast gene. Deletion of DNA sequences between -291 and -273 specifically eliminated derepression of CIT1, and destroyed one of two closely-spaced, potential binding sites for the HAP2,3,4 transcriptional activator protein. Ten-base-pair block substitutions in the region -367 to -348 reduced glucose-repressed expression. Thus, it appears that distinct DNA sequences upstream of CIT1 activate expression in glucose-repressed and derepressed cells. Possible mechanisms of regulation by glutamate plus glucose, are discussed.
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PMID:Distinct upstream activation regions for glucose-repressed and derepressed expression of the yeast citrate synthase gene CIT1. 792 3

The yeast nuclear gene CIT1 encodes mitochondrial citrate synthase, which catalyses the first and rate-limiting step of the tricarboxylic acid (TCA) cycle. Transcription of CIT1 is subject to glucose repression. Mutations in HAP2, HAP3 or HAP4 block derepression of a CIT1-lacZ gene fusion. The HAP2,3,4 transcriptional activator also activates nuclear genes encoding components of the mitochondrial electron transport chain, and thus it co-ordinates derepression of two major mitochondrial functions. Two DNA sequences resembling the consensus HAP2,3,4-binding site (ACCAATNA) are located at approximately -310 and -290, upstream of the CIT1 coding sequence. Deletion and mutation analysis indicates that the -290 element is critical for activation by HAP2,3,4. Glucose-repressed expression of CIT1 is largely independent of HAP2,3,4, is repressed by glutamate, and requires a DNA sequence between -367 and -348. Evidence is presented for a second HAP2,3,4-independent activation element located just upstream and overlapping the -290 HAP2,3,4 element.
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PMID:The HAP2,3,4 transcriptional activator is required for derepression of the yeast citrate synthase gene, CIT1. 798 86

We identified a gene of the fungal pathogen Candida albicans, designated EFG1, whose high-level expression stimulates pseudohyphal morphogenesis in the yeast Saccharomyces cerevisiae. In a central region the deduced Efg1 protein is highly homologous to the StuA and Phd1/Sok2 proteins that regulate morphogenesis of Aspergillus nidulans and S. cerevisiae, respectively. The core of the conserved region is homologous to the basic helix-loop-helix (bHLH) motif of eukaryotic transcription factors, specifically to the human Myc and Max proteins. Fungal-specific residues in the bHLH domain include the substitution of an invariant glutamate, responsible for target (E-box) specificity, by a threonine residue. During hyphal induction EFG1 transcript levels decline to low levels; downregulation is effected at the level of transcriptional initiation as shown by a EFG1 promoter-LAC4 fusion. A strain carrying one disrupted EFG1 allele and one EFG1 allele under the control of the glucose-repressible PCK1 promoter forms rod-like, pseudohyphal cells, but is unable to form true hyphae on glucose-containing media. Overexpression of EFG1 in C. albicans leads to enhanced filamentous growth in the form of extended pseudohyphae in liquid and on solid media. The results suggest that Efg1p has a dual role as a transcriptional activator and repressor, whose balanced activity is essential for yeast, pseudohyphal and hyphal morphogenesis of C. albicans. Functional analogies between Efg1p and Myc are discussed.
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PMID:Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. 915 24

Mutations in the gene encoding the Pit-1 transcriptional activator interfere with the embryologic determination and ultimate functions of anterior pituitary cells that produce growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH). Central hypothyroidism is often the presenting feature of combined pituitary hormone deficiency (CPHD), but it is not detected in screening programs that rely upon elevation of TSH. We report a child whose hypothyroidism was recognized clinically at age 6 weeks, and subsequently found to have GH and Prl as well as TSH deficiency. With thyroxine and GH replacement he has reached the 70th percentile for height and has normal intelligence. Molecular analysis of genomic DNA for Pit-1 revealed the presence of compound heterozygous recessive mutations: a nonsense mutation in codon 172 and a novel missense mutation substituting glycine for glutamate at codon 174. This case is the first demonstration of CPHD due to compound heterozygous Pit-1 point mutations, as most reported cases of the CPHD phenotype involve either the dominant negative R271W allele or homozygosity for recessive Pit-1 mutations. Therefore, in cases of CPHD, the possibilities of compound heterozygosity for two different Pit-1 mutations, or homozygosity for mutations in the epigenetic gene, Prop-1, should be considered.
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PMID:Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene. 948 79

The GvpE protein involved in the regulation of gas vesicles synthesis in halophilic archaea has been identified as the transcriptional activator for the promoter located upstream of the gvpA gene encoding the major gas vesicle structural protein GvpA. A closer inspection of the GvpE protein sequence revealed that GvpE resembles basic leucine-zipper proteins typically involved in the gene regulation of eukarya. A molecular modelling study of the C-terminal part implied a cluster of basic amino acid residues constituting the DNA-binding site (DNAB) followed by an amphiphilic helix, suitable for the formation of a leucine-zipper structure within a GvpE dimer. The model of a GvpE dimer docked onto DNA indicated that the side-chains of the basic residues could perfectly interact with the negatively charged phosphate groups of the DNA backbone. Substitution of three basic amino acid residues of this putative DNAB by alanine and/or glutamate generated mutated GvpE proteins. None of these was able to activate the c-gvpA promoter in vivo, indicating that these basic residues are required for GvpE activity. This identification of an archaeal gene regulator displaying similarity to eukaryal regulatory proteins implies that the basic transcription machinery of eukarya and archaea are closely related, and that the regulatory proteins have evolved according to common principles.
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PMID:The transcriptional activator GvpE for the halobacterial gas vesicle genes resembles a basic region leucine-zipper regulatory protein. 964 59

The VP16 protein of herpes simplex virus is a potent transcriptional activator of the viral immediate early genes. The transcriptional activation region of VP16 can be divided into two functional subregions, here designated VP16N (comprising amino acids 413-456) and VP16C (amino acids 450-490). Assays of VP16C mutants resulting from both random and alanine-scanning mutagenesis indicated that the sidechains of three phenylalanines (at positions 473, 475 and 479) and one acidic residue (glutamate 476) are important for transcriptional activation. Aromatic and bulky hydrophobic amino acids were effective substitutes for each of the three Phe residues, whereas replacement with smaller or polar amino acids resulted in loss of transcriptional function. In contrast, many changes were tolerated for Glu476, including bulky hydrophobic and basic amino acids, indicating that the negative charge at this position contributes little to the function of this subregion. Similar relative activities for most of the mutants were observed in yeast and in mammalian cells, indicating that the structural requirements for this activation region are comparable in these two species. These results reinforce the hypothesis that bulky hydrophobic residues, not acidic residues, are most critical for the activity of this 'acidic' transcriptional activation region.
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PMID:Mutational analysis of a transcriptional activation region of the VP16 protein of herpes simplex virus. 974 54


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