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)

To investigate the mechanisms involved in expression of the Drosophila melanogaster engrailed gene, we purified GAGA protein, one of several putative transcriptional activator proteins that binds to the proximal region of the engrailed promoter. Antibodies raised against GAGA protein were used to demonstrate that the protein is present in all nuclei of young embryos. We isolated cDNA clones encoding GAGA protein in which a putative 519-codon open reading frame contains general sequence motifs characteristic of other transcription factors. These include stretches of polyglutamine, a 60-amino-acid region with 18 (30%) lysine or arginine residues, and a single putative zinc finger motif. In addition, a 120-residue N-terminal region shares significant sequence homology with several other known Drosophila transcription factors, including those encoded by Broad Complex and tramtrack. Up to 35-fold GAGA protein-dependent stimulation of transcription in Schneider line 2 tissue culture cells was observed after transfection of GAGA protein-encoding sequences. The GAGA gene is present in one copy in the Drosophila genome, at cytological location 70EF, and it encodes RNAs which vary in size between 2.4 and 4.4 kb.
Mol Cell Biol 1993 Dec
PMID:Isolation of cDNAs encoding the Drosophila GAGA transcription factor. 750 78

Binding of type I interferons (IFNs) to their receptors induces rapid tyrosine phosphorylation of multiple proteins, including the alpha and beta subunits of the receptor, the polypeptides that form the transcriptional activator ISGF3 alpha (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases. In this report, we demonstrate that the alpha subunit of the type I IFN receptor (IFN-R) corresponds to the product of a previously cloned receptor subunit cDNA and, further, that the p135tyk2 tyrosine kinase directly binds and tyrosine phosphorylates this receptor subunit. Glutathione S-transferase (GST) fusion proteins encoding the different regions of the cytoplasmic domain of the alpha subunit can bind the p135tyk2 contained in human cell lysates. The association between the alpha subunit and Tyk2 was demonstrated by immunoblotting with anti-Tyk2 and antiphosphotyrosine antibodies and by using an in vitro kinase assay. Analogous experiments were then performed with recombinant baculoviruses encoding constitutively active Jak family tyrosine kinases. In this case, p135tyk2, but not Jak-1 or Jak-2 protein, binds to the GST-IFN-R proteins, suggesting that the interaction between these two proteins is both direct and specific. We also demonstrate that Tyk2, from extracts of either IFN alpha-treated human cells or insect cells infected with the recombinant baculoviruses, can catalyze in vitro phosphorylation of GST-IFN-R protein in a specific manner. Deletion mutants of the GST-IFN-R protein were used to localize both the binding and tyrosine phosphorylation site(s) to a 46-amino-acid juxtamembrane region of the alpha subunit, which shows sequence homology to functionally similar regions of other cytokine receptor proteins. These data support the hypothesis that the Tyk2 protein functions as part of a receptor complex to initiate intracellular signaling in response to type I IFNs.
Mol Cell Biol 1994 Dec
PMID:Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. 752 54

The Salmonella typhimurium fimA gene is controlled by several ancillary fim genes. One of these genes, fimZ, appears to be involved in increasing the expression of fimA. A fimZ mutant of S. typhimurium was constructed by allelic exchange, and this mutant was found to be nonfimbriate. The fimZ mutant demonstrated decreased levels of fimA expression compared with the parental strain when both were grown under conditions favoring fimbrial expression. An examination of the predicted amino acid sequence, deduced from the nucleotide sequence of fimZ, indicated that the FimZ polypeptide possessed a DNA binding motif. Bacterial lysates, derived from strains transformed with recombinant plasmids possessing a fimZ gene, demonstrated DNA binding activity with a fragment containing the fimA promoter. Lysates without a FimZ polypeptide did not exhibit any binding activity. These data are consistent with FimZ being a transcriptional activator of fimA, and FimZ acts by binding to the promoter region.
J Bacteriol 1995 Dec
PMID:Construction and characterization of a fimZ mutant of Salmonella typhimurium. 759 79

In Vibrio fischeri, the autoinducer N-3-oxohexanoyl-L-homoserine lactone (AI-1) governs the cell density-dependent induction of the luminescence operon via the LuxR transcriptional activator. The synthesis of AI-1 from bacterial metabolic intermediates is dependent on luxI. Recently, we found a second V. fischeri autoinducer molecule, N-octanoyl-L-homoserine lactone (AI-2), that in E. coli also activates the luminescence operon via LuxR. A locus independent of luxI was identified as being required for AI-2 synthesis. This 2.7-kb ain (autoinducer) locus was characterized by transposon insertion mutagenesis, deletion and complementation analysis, and DNA sequencing. A single 1,185-bp gene, ainS, was found to be the sole exogenous gene necessary for the synthesis of AI-2 in Escherichia coli. In addition, a V. fischeri ainS mutant produced AI-1 but not AI-2, confirming that in its native species ainS is specific for the synthesis of AI-2. ainS is predicted to encode a 45,580-Da protein which exhibits no similarity to LuxI or to any of the LuxI homologs responsible for the synthesis of N-acyl-L-homoserine lactones in a variety of other bacteria. The existence of two different and unrelated autoinducer synthesis genes suggests the occurrence of convergent evolution in the synthesis of homoserine lactone signaling molecules. The C-terminal half of AinS shows homology to a putative protein in Vibrio harveyi, LuxM, which is required for the synthesis of a V. harveyi bioluminescence autoinducer. Together, AinS and LuxM define a new family of autoinducer synthesis proteins. Furthermore, the predicted product of another gene, ainR, encoded immediately downstream of ainS, shows homology to LuxN, which is similarly encoded downstream of luxM in V. harveyi and proposed to have sensor/regulator functions in the bioluminescence response to the V. harveyi auto inducer. This similarity presents the possibility that AI-2, besides interacting with LuxR, also interacts with AinR under presently unknown conditions.
J Bacteriol 1995 Dec
PMID:AinS and a new family of autoinducer synthesis proteins. 759 89

Phosphorylation of translation initiation factor 2 alpha is a highly conserved mechanism for down-regulating protein synthesis in response to starvation or stress. The yeast eIF-2 alpha kinase GCN2 is stimulated by deprivation for amino acids or purines. In addition to inhibiting general protein synthesis, GCN2 specifically stimulates translation of GCN4, a transcriptional activator of amino acid biosynthetic genes. HRI is an eIF-2 alpha kinase that is activated in rabbit reticulocytes by heme-deprivation and stress conditions that elicit the heat-shock response. The eIF-2 alpha kinase DAI is activated by double-stranded RNA during viral infections and is an important component of the interferon response. DAI has also been implicated as a tumor suppressor. These protein kinases provide an important means of coupling the rate of protein synthesis and cell division to environmental conditions.
Semin Cell Biol 1994 Dec
PMID:The eIF-2 alpha kinases: regulators of protein synthesis in starvation and stress. 771 Dec 90

The PilR protein of Pseudomonas aeruginosa is a transcriptional activator of the pilin gene and belongs to a two-component sensor-regulator family. PilR was overproduced by fusing pilR to the gene for the maltose-binding protein (malE), yielding a MalE-PilR hybrid protein. The plasmid with the malE-pilR fusion, when introduced into a non-piliated pilR mutant strain of P. aeruginosa, restored piliation, indicating that the hybrid protein retains PilR function in vivo. The MalE-PilR protein was purified from Escherichia coli and used in a series of DNA-binding studies. A specific pilin promoter-binding activity of MalE-PilR was observed in a gel retardation assay. Subsequent DNase I footprinting analysis revealed a 40 bp PilR-binding site located at the -120 to -80 region, relative to the transcriptional start site of the pilin gene. This PilR-binding region consists of a nine-base sequence and three consensus sequences of 5'-(N)4-6C/GTGTC-3', in a tandem array in which the first 7-9 bp are bound by the PilR on the non-coding strand, leaving the last two nucleotides (TC) unbound. On the coding strand, PilR binds to sequences complementary to the two middle consensus sequences of the non-coding strand. A sequence similar to the NifA recognition site (5'-TGT-(N)11-ACA-3') is also found within the PilR-binding region. Deletion analysis and disruption of the individual consensus PilR-binding sequences by site-directed mutagenesis revealed that all four PilR-binding sites are absolutely required for the PilS/PilR-mediated pilin gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Microbiol 1994 Dec
PMID:PilR, a transcriptional regulator of piliation in Pseudomonas aeruginosa, binds to a cis-acting sequence upstream of the pilin gene promoter. 771 43

We have tried to optimize the galactose-inducible gene expression system for the overproduction of the potent thrombin-specific inhibitor, hirudin, in a genetically engineered yeast, Saccharomyces cerevisiae. The expression and secretion of hirudin were directed by the galactose-inducible promoter, GAL10, and the mating factor alpha pre-pro leader sequence. The initial hirudin expression level in shake-flask culture was 2.3 mg 1-1. Modification of the expression vector and optimization of culture conditions, including the induction conditions, improved the level of hirudin gene expression and secretion into the culture supernatant more than 20-fold (50 mg 1-1) in a 4-1 scale batch cultivation. The expression and secretion level of hirudin seemed to be partially dependent on cell growth when galactose was used as a carbon source. Overexpression of the transcriptional activator, GAL4, appeared to have only negative effects on the expression of the hirudin gene and lacZ directed by the GAL10 promoter in the strain used in this study, unlike the previously reported examples. The complex medium containing yeast extract used for the increase of the cell mass and hirudin level did not show any detrimental effect on plasmid stability and did not complicate the downstream purification of hirudin from the culture supernatant. Moreover, the complex medium could greatly improve the hirudin productivity and reduce the degradation of hirudin produced in the culture supernatants.
Appl Microbiol Biotechnol 1994 Dec
PMID:Optimization of the expression system using galactose-inducible promoter for the production of anticoagulant hirudin in Saccharomyces cerevisiae. 776 34

The soil bacterium Rhizobium meliloti fixes dinitrogen when associated with root nodules formed on its plant host, Medicago sativa (alfalfa). The expression of most of the known genes required for nitrogen fixation (nif and fix genes), including the structural genes for nitrogenase, is induced in response to a decrease in oxygen concentration. Induction of nif and fix gene expression by low oxygen is physiologically relevant because a low-oxygen environment is maintained in root nodules to prevent inactivation of the highly oxygen-sensitive nitrogenase enzyme. The genes responsible for sensing and transducing the low oxygen signal, fixL and fixJ, encode proteins (FixL and FixJ, respectively) that are homologous to a large family of bacterial proteins involved in signal transduction, the two component regulatory system proteins. The two components consist of a sensor protein, to which FixL is homologous, and a response regulator protein, to which FixJ is homologous. The sensor protein respond to an activating signal by autophosphorylating and then transferring the phosphate to its cognate response regulator protein. The phosphorylated response regulator, which is often a transcriptional activator, is then able to activate its target. A cascade model of nif and fix gene regulation in R. meliloti has been proposed, whereby FixL acts as an oxygen sensor as the initial event in the cascade and transmits this information to FixJ. FixJ, which possesses a putative helix-turn-helix DNA-binding motif, then activates transcription of the nifA and fixK genes. The nifA and fixK gene products, are transcriptional activators of at least 14 other nif and fix genes.
Microbiologia 1994 Dec
PMID:Genetic regulation of nitrogen fixation in Rhizobium meliloti. 777 92

Upon entry into a host cell, retroviruses direct the reverse transcription of the viral RNA genome and the establishment of an integrated proviral DNA. The retroviral integrase protein (IN) is responsible for the insertion of the viral DNA into host chromosomal targets. The two-hybrid system was used to identify a human gene product that binds tightly to the human immunodeficiency virus-type 1 (HIV-1) integrase in vitro and stimulates its DNA-joining activity. The sequence of the gene suggests that the protein is a human homolog of yeast SNF5, a transcriptional activator required for high-level expression of many genes. The gene, termed INI1 (for integrase interactor 1), may encode a nuclear factor that promotes integration and targets incoming viral DNA to active genes.
Science 1994 Dec 23
PMID:Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. 780 Nov 19

The cDNA coding for the Xenopus laevis homolog of the transcriptional activator/repressor protein delta/YY1 was isolated from a lambda gt11 oocyte cDNA library. The deduced aminoacid sequence shows that the four zinc fingers of the DNA binding domain are 99% conserved when compared to the mouse (delta) and 95% to the human (YY1) proteins, while differences are found in the N-terminal region. In particular, the long run of consecutive glycines and histidines of delta and YY1 is missing. The protein, named FIII/YY1, was overexpressed into Xenopus oocytes from the cDNA under direction of the L14 rp-promoter and found to share antigenic and DNA-binding properties with the oocyte endogenous protein binding to the first exon of the X.laevis ribosomal protein genes (rp-genes) L1 and L14.
Biochem Biophys Res Commun 1994 Dec 15
PMID:Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein binding to the first exon of L1 and L14 ribosomal protein genes. 780 55


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