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)

Acquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV). The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B), and this transcriptional activator appears to regulate HIV activation. Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation. The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS. Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml). The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine. These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics.
Biochem Biophys Res Commun 1992 Dec 30
PMID:Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. 148 76

A promoter probe vector, which utilized the lux AB genes from Vibrio fischeri as reporters of gene expression, was constructed for use in Listeria monocytogenes. Using this system gene expression can be monitored non-destructively and in real-time, simply by measuring cellular bioluminescence. Derivatives of the promoter probe were constructed that contained the cloned promoters from the hlyA and plcA genes of L. monocytogenes. The activity of these promoters was dependent on the transcriptional activator PrfA. Accordingly, in a strain containing an intact copy of the prfA gene, expression from both the hlyA and plcA promoters was 25-45-fold higher than in prfA mutants. Heat shock was identified as an environmental signal which induced expression of hlyA and plcA. Conversely, oxidative stress had no effect upon the expression of the virulence factors. In addition, the composition of the growth media was found to have a dramatic effect upon the expression of hlyA and plcA, suggesting the presence of an unidentified signal which may regulate induction of expression of virulence genes in L. monocytogenes.
J Gen Microbiol 1992 Dec
PMID:The use of bacterial luciferase for monitoring the environmental regulation of expression of genes encoding virulence factors in Listeria monocytogenes. 148 29

Eukaryotic transcriptional activators are believed to stimulate transcription through direct and/or indirect interactions with one or more of the general transcription factors. We show here that the Zta transcriptional activator protein encoded by the Epstein-Barr virus makes direct physical contact with the basic transcription factor TFIID. Both Zta and TFIID were expressed in and purified from Escherichia coli. Zta stabilized the binding of TFIID to Zta-responsive promoters as assayed by gel electrophoresis mobility-shift and immunoprecipitation of radiolabeled promoter DNA. A deletion mutant of Zta that failed to activate transcription failed to stabilize TFIID binding. DNase I footprinting showed that Zta reduced the dissociation rate of TFIID bound to the TATA element. Protein blotting and immunoprecipitation experiments demonstrated that TFIID and Zta also interact in the absence of promoter DNA. The amino acid residues 25-86 of Zta were essential for the stable association with TFIID and were shown to be required for trans-activation in vivo. We propose that Zta stimulates transcription, in part, by direct physical contact with the conserved domain of TFIID and the formation of a stable Zta-TFIID-promoter complex.
Genes Dev 1991 Dec
PMID:The Zta trans-activator protein stabilizes TFIID association with promoter DNA by direct protein-protein interaction. 166 Dec 58

Several epidemiological studies have demonstrated a link between chronic B virus infection and primary hepatocellular carcinoma (PHC). HBV DNA sequence integrations into the host cell genome have often been observed in hepatocarcinoma tissues. However, since only in a few cases of PHC the target of HBV-DNA insertion has been identified, alternative mechanisms for HBV-induced hepatocyte transformation have been investigated. Like many other DNA viruses, the hepatitis B virus bears a transactivational potential. Both full length and truncated versions of HBV X protein are able to influence the expression of cellular nuclear protooncogenes c-fos and c-myc. A second transcriptional activator is encoded by the PreS/S region of HBV, but its activity on viral and cellular genes become evident only after dislocations from its downstream sequences. Thus, HBV is able to influence infected cell growth and differentiation using both native proteins, newly generated truncated proteins and virus-cell fusion polypeptides.
Ital J Gastroenterol 1991 Dec
PMID:Hepatitis B virus and hepatocellular carcinoma: a possible role for the viral transactivators. 166 93

Taz1 is a hybrid signal-transducing membrane receptor between Tar, an aspartate chemoreceptor, and EnvZ, an osmosensor of Escherichia coli that is able to induce ompC expression by phosphorylating OmpR (a transcriptional activator) in response to aspartate. When the Taz1 His-277, the proposed autophosphorylation site in the cytoplasmic EnvZ domain, was replaced with a valine residue, the mutant Taz1 was unable to induce ompC expression. Similarly, when approximately two-thirds of the EnvZ domain was deleted, Taz1 was nonfunctional. However, when these two defective Taz1 proteins were coexpressed in a cell, ompC was constitutively expressed. Coinciding with this result, two mutant Taz1 molecules were able to intermolecularly complement each other to restore the OmpR kinase activity but not phosphatase activity in vitro. The identical result was also obtained with EnvZ. The present results suggest that the autophosphorylation of Taz1 and EnvZ is an intermolecular phosphorylation reaction, requiring formation of a dimer (or oligomer), and that ligand-dependent ompC expression requires not only kinase but also phosphatase activity.
Proc Natl Acad Sci U S A 1991 Dec 15
PMID:Intermolecular complementation between two defective mutant signal-transducing receptors of Escherichia coli. 166 80

The Tax protein of the human T-cell leukemia virus type I (HTLV-I) serves as a potent transcriptional activator of its own long terminal repeat as well as select cellular genes, including interleukin-2 and the alpha subunit of the interleukin-2 receptor. Tax activation of these two growth-related genes appears to involve the induced nuclear expression of DNA-binding proteins that specifically engage related kappa B enhancer elements present in the 5' regulatory regions of these genes. In human T cells, kappa B enhancer-binding activity has been discerned as an unexpectedly large family of UV cross-linked nucleoprotein adducts, termed p50, p55, p75, and p85. The protein components of each of these DNA-protein adducts have been shown to share structural similarity with the v-rel oncogene product. The p55 adduct is composed of the 50-kDa subunit of NF-kappa B derived from a 105-kDa precursor polypeptide, while the p50 adduct contains a smaller protein that is closely related to NF-kappa B p50. The p75 adduct contains the 65-kDa subunit of NF-kappa B, while the p85 adduct is composed of the human c-rel proto-oncogene product. We now demonstrate that HTLV-I Tax, in the absence of other viral pX gene products, is capable of inducing the nuclear expression of all four of these kappa B-binding proteins in human T cells, with most marked effects involving c-Rel and NF-kappa B p65. Tax induction of the nuclear expression of c-Rel and NF-kappa B p50 is regulated, at least in part, at a pretranslational level involving increases in c-rel and NF-kappa B p105 mRNA expression. To study the pattern of expression of these kappa B-specific proteins in cells infected with the whole HTLV-I, seven cloned HTLV-I-infected T-cell lines were established from the peripheral blood of patients with adult T-cell leukemia. Of note, only three of these seven cell lines produced Tax, and c-rel mRNA and nuclear protein expression was confined to these three cell lines. In contrast, NF-kappa B p50 and NF-kappa B p65 were constitutively expressed in the nuclei of all seven of the HTLV-I-infected cell lines, even in the absence of detectable Tax or other viral gene expression. These findings raise the possibility of an alternate, Tax-independent pathway for the induced nuclear expression of NF-kappa B p50 and NF-kappa B p65 following HTLV-I infection.
J Virol 1991 Dec
PMID:Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of kappa B enhancer-binding proteins: evidence for a pretranslational component of regulation. 171 36

The fadR gene of Escherichia coli encodes a protein that acts as a negative regulator (repressor) of the inducible beta-oxidation pathway. We report that the FadR protein also functions as a positive transcriptional activator of the fabA gene, which encodes the enzyme introducing the double bond of the unsaturated fatty acids of E. coli.
J Mol Biol 1991 Dec 20
PMID:Escherichia coli transcription factor that both activates fatty acid synthesis and represses fatty acid degradation. 172 55

Previously, we isolated and characterized six Bacillus subtilis ada mutants that were hypersensitive to methylnitroso compounds and deficient in the adaptive response to alkylation. Cloning of the DNA complementing the defects revealed the presence of an ada operon consisting of two tandem and partially overlapping genes, adaA and adaB. The two genes encoded proteins with methylphosphotriester-DNA methyltransferase and O6-methylguanine-DNA methyltransferase activities, respectively. To locate the six mutations, the ada operon was divided into five overlapping regions of about 350 bp. The fragments of each region were amplified by polymerase chain reaction and analyzed by gel electrophoresis to detect single-strand conformation polymorphism. Nucleotide sequences of the fragments exhibiting mobility shifts were determined. Three of the mutants carried sequence alterations in the adaA gene: the adaA1 and adaA2 mutants had a one-base deletion and insertion, respectively, and the adaA5 mutant had a substitution of two consecutive bases causing changes of two amino acid residues next to the presumptive alkyl-accepting Cys-85 residue. Three mutants carried sequence alterations in the adaB gene: the adaB3 mutant contained a rearrangement, the adaB6 mutant contained a base substitution causing a change of the presumptive alkyl-accepting Cys-141 to Tyr, and the adaB4 mutant contained a base substitution changing Leu-167 to Pro. The adaB mutants produced ada transcripts upon treatment with low doses of alkylating agents, whereas the adaA mutant did not. We conclude that the AdaA protein functions as the transcriptional activator of this operon, while the AdaB protein specializes in repair of alkylated residues in DNA.
J Bacteriol 1991 Dec
PMID:Molecular analysis of Bacillus subtilis ada mutants deficient in the adaptive response to simple alkylating agents. 174 39

We have recently shown that the human apoA-II promoter contains a set of 11 distal regulatory elements between nucleotides -903 and -255 and three proximal regulatory elements between nucleotides -126 and -33 that are essential for hepatic and intestinal transcription of the apoA-II gene (Chambaz, J., Cardot, P., Pastier, D., Zannis, V. I., and Cladaras, C. (1991) J. Biol. Chem. 266, 11676-11685). Deletion or nucleotide substitution analysis has shown that alterations in elements L (nucleotides -803 to -773) and K (nucleotides -760 to -743) reduced hepatic transcription to 25 and 20% and intestinal transcription to 8 and 4% of control, respectively, as measured by chloramphenicol acetyltransferase assays, indicating that these elements play an important regulatory role. Nucleotide substitutions in element AB (nucleotides -65 to -33) reduced hepatic and intestinal transcription to 60 and 36% of control, respectively. The factors that recognize regulatory regions L, K, and AB were analyzed by DNA binding gel electrophoretic and competition assays. This analysis has shown that elements AB, K, and L bind with different affinities to a newly characterized heat-stable factor, CIIIB1, which is a transcriptional activator of the human apoC-III gene (Ogami, K., Kardassis, D., Cladaras, C., and Zannis, V. I. (1991) J. Biol. Chem. 266, 9640-9646). In addition, elements AB and K bind a heat-labile activity, designated AIIAB1, and element L binds to several CCAAT box binding activities. Mutations in domain L that prevented the binding of CCAAT box binding activities reduced both hepatic and intestinal transcription to 30% of control, indicating the importance of these factors in transcription. Simultaneous nucleotide substitutions that prevented the binding of CIIIB1 activity in elements AB, K, and L reduced hepatic and intestinal transcription to 7 and 6% of control, respectively, suggesting that the synergistic interaction of CIIIB1 (bound to the proximal and distal regulatory elements) with CCAAT box proteins (bound to element L) can modulate the level of transcription of the human apoA-II gene.
J Biol Chem 1991 Dec 25
PMID:Regulation of the human ApoA-II gene by the synergistic action of factors binding to the proximal and distal regulatory elements. 176 46

The Vibrio fischeri luminescence genes are activated by an autoinducer and the 250-amino acid residue LuxR protein. To develop a general view of LuxR structure and function, a set of luxR 5'-deletion mutations was generated. Ten luxR mutant plasmids encoding active LuxR proteins with deletions ranging from residues 2-5 (delta 2-5) to residues 2-182 (delta 2-182) were studied. The degree of transcriptional activation of luminescence genes by the truncated LuxR proteins ranged from 0.01% to greater than 200% of the wild-type level. LuxR proteins with small deletions (up to delta 2-20) were active and remained autoinducer-dependent, LuxR proteins with deletions between residues 2-58 and 2-138 showed low activity and were not affected by autoinducer, and LuxR proteins with large deletions such as the delta 2-162 protein were highly active and autoinducer-independent. However, proteins with deletions equal to or greater than delta 2-20 were unable to autoregulate luxR. Our data indicate there is a C-terminal LuxR domain capable of functioning as a transcriptional activator. We suggest that an N-terminal region of LuxR starting between residues 20 and 58 and extending to the region of residues 138-162 masks the activator function of the C-terminal domain. Residues prior to position 20 are needed for autoregulatory function. Experiments showing that wild-type luxR is dominant over luxR genes coding the delta 2-58 through delta 2-138 proteins indicate the N-terminal arm masks lux DNA binding.
Proc Natl Acad Sci U S A 1991 Dec 15
PMID:The C-terminal region of the Vibrio fischeri LuxR protein contains an inducer-independent lux gene activating domain. 176 27


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