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

The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.
Mol Cell Biol 1996 Sep
PMID:Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function. 875 54

The general transcription factor TFIID is composed of the TATA-box-binding protein (TBP) and a set of TBP-associated factors (TAFIIs). In vitro, TAFIIs are required for activated transcription, and have been proposed to be obligatory targets of transcriptional activator proteins (activators)2. The function of TAFIIs has not been investigated systematically in vivo. A Saccharomyces cerevisiae TAFII complex (yTAFII complex) has been identified that shares functional and structural similarities with higher eukaryotic TFIID. In particular, most yTAFIIs are the homologue of a higher eukaryotic TAFII. Here we report that inactivation or depletion of six different yTAFIIs, including the core yTAFII, that contacts TBP, does not compromise transcriptional activation. We conclude that in vivo, activated transcription of many genes can occur in the absence of functional yTAFIIS, and that in these instances another transcription component(s) must be the target of the activator.
Nature 1996 Sep 12
PMID:Transcription activation in cells lacking TAFIIS. 877 74

Carboxy-terminally truncated hepatitis B virus (HBV) middle surface proteins (MHBst) show a transcriptional activator function. Two different subtypes of MHBst activators can be distinguished: an ER-localized type, represented here by MHBst76 (truncated at amino acid 76), and a cytosol-localized type, represented here by MHBst63. To characterize the MHBst activator on the protein level and to analyze posttranslational modifications, we established recombinant baculoviruses encoding for fusion proteins of MHBst76 or MHBst63 and of an amino terminal hexa-his tag. Both proteins could be obtained in high purity by affinity chromatography using Ni-nitrilo-tri-acetate agarose. In addition, 6H-MHBst76 was also isolated from transiently transfected HepG2 cells. Both the Spodoptera frugiperda (Sf9) cell-derived and the HepG2 cell-derived MHBst proteins were found to be unglycosylated. A detailed analysis of Sf9 cell-derived 6H-MHFBst76 by electrospray-ionization mass spectrometry showed that a fraction of this protein is N-terminally acetylated and phosphorylated or sulfated. Electric-field-mediated transfer of the highly purified proteins into reporter cells demonstrated that the isolated proteins are functional transcriptional activators. These experiments further showed that Sf9 cell-derived and HepG2 cell-derived 6H-MHBst do not differ in their functionality. This system allowed production and purification of functional 6H-MHBst in amounts sufficient enough to allow a further detailed analysis of MHBst activators on the protein level.
Hepatology 1996 Sep
PMID:Isolation of highly purified, functional carboxy-terminally truncated hepatitis B virus middle surface protein activators from eucaryotic expression systems. 878 14

Pediatric alveolar rhabdomyosarcoma is characterized by a chromosomal translocation that fuses parts of the PAX3 and FKHR genes. PAX3 codes for a transcriptional regulator that controls developmental programs, and FKHR codes for a forkhead-winged helix protein, also a likely transcription factor. The PAX3-FKHR fusion product retains the DNA binding domains of the PAX3 protein and the putative activator domain of the FKHR protein. The PAX3-FKHR protein has been shown to function as a transcriptional activator. Using the RCAS retroviral vector, we have introduced the PAX3-FKHR gene into chicken embryo fibroblasts. Expression of the PAX3-FKHR protein in these cells leads to transformation: the cells become enlarged, grow tightly packed and in multiple layers, and acquire the ability for anchorage-independent growth. This cellular transformation in vitro will facilitate studies on the mechanism of PAX3-FKHR-induced oncogenesis.
Proc Natl Acad Sci U S A 1996 Sep 03
PMID:The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture. 879 Apr 12

Hydrogen peroxide (H2O2) imposes an oxidative stress to Escherichia coli that is manifested by oxidation of glutathione and related redox-sensitive targets. OxyR is a thiol-containing transcriptional activator whose oxidation controls the expression of genes involved in H2O2 detoxification. Here we report that certain S-nitrosothiols (RSNOs) impose what we term a "nitrosative stress" to E. coli, evidenced by lowering of intracellular thiol and the transcriptional activation of OxyR by S-nitrosylation. This cellular and genetic response determines the metabolic fate of RSNOs and thereby contributes to bacterial rescue from stasis. Our studies reveal that signaling by S-nitrosylation can extend to the level of transcription and describe a metabolic pathway that constitutes an adaptation to nitrosative stress.
Cell 1996 Sep 06
PMID:Nitrosative stress: activation of the transcription factor OxyR. 879 19

Genes whose expression is regulated by sulfate starvation in Escherichia coli were identified by generating random translational lacZ fusions in the chromosome with the lambda placMu9 system. Nine lacZ fusion strains which expressed beta-galactosidase after growth under sulfate starvation conditions but not after growth in the presence of sulfate were found. These included two strains with insertions in the dmsA and rhsD genes, respectively, and seven strains in which the insertions were located within a 1.8-kb region downstream of hemB at 8.5 minutes on the E. coli chromosome. Analysis of the nucleotide sequence of this region indicated the presence of four open reading frames designated tauABCD. Disruption of these genes resulted in the loss of the ability to utilize taurine (2-aminoethanesulfonate) as a source of sulfur but did not affect the utilization of a range of other aliphatic sulfonates as sulfur sources. The TauA protein contained a putative signal peptide for transport into the periplasm; the TauB and TauC proteins showed sequence similarity to ATP-binding proteins and membrane proteins, respectively, of ABC-type transport systems; and the TauD protein was related in sequence to a dichlorophenoxyacetic acid dioxygenase. We therefore suggest that the proteins encoded by tauABC constitute an uptake system for taurine and that the product of tauD is involved in the oxygenolytic release of sulfite from taurine. The transcription initiation site was detected 26 to 27 bp upstream of the translational start site of tauA. Expression of the tauD gene was dependent on CysB, the transcriptional activator of the cysteine regulon.
J Bacteriol 1996 Sep
PMID:Identification of sulfate starvation-regulated genes in Escherichia coli: a gene cluster involved in the utilization of taurine as a sulfur source. 880 33

MalT is the transcriptional activator of the Escherichia coli maltose regulon. Several lines of evidence suggest that MalT might act by interacting with RNA polymerase. Here, we show that 'MalT, the DNA-binding domain of MalT, activates transcription. In order to identify amino acids of 'MalT playing a specific role in activation, and therefore possibly involved in the putative contact(s) with RNA polymerase, we developed a double screen to isolate mutations of the 'malT gene affecting activation by 'MalT without impairing its DNA-binding affinity. The effect of the mutations thus obtained on activation was assessed in vivo. This strategy essentially pointed to serine 834 and glutamine 876 of the MalT amino acid sequence as specifically involved in activation. Various 'MalT derivatives substituted at positions 834 or 876 were purified and tested in vitro for their DNA-binding affinity, as well as for their activation ability. Together, the results obtained clearly show that serine 834 and glutamine 876 are important for activation by 'MalT but not for DNA-binding. We argue that these amino acid residues are possibly solvent-exposed and propose that they act by contacting RNA polymerase.
J Mol Biol 1996 Sep 13
PMID:Two amino acid residues from the DNA-binding domain of MalT play a crucial role in transcriptional activation. 880 74

Two Bradyrhizobium japonicum nolA mutants were constructed and used to test the functional role of NolA in nodulation. Contrary to the previous hypothesis that NolA acts as a repressor of nod gene transcription, the expression of a nodD1-lacZ or nodY-lacZ fusion in the nolA mutant strains was similar to that found in the wild type. However, NolA does appear to act as a transcriptional regulatory protein since it is required for its own expression, as well as that of nodD2. Expression of NodD2 from a constitutive promoter led to a significant reduction in nodC-lacZ activity. Therefore, the repression of nod gene expression by NolA is likely an indirect effect, perhaps mediated by other genes (e.g., nodD2) that are regulated by NolA. When inoculated onto soybean roots, the nolA mutant strains showed only a slight delay in nodulation as compared to the wild type. However, the mutant strains were grossly defective in nodulation and nitrogen fixation on cowpea plants. Microscopic examination of soybean nodules induced by the nolA mutant strains showed developmental and morphological characteristics similar to nodules formed by the wild type with only a slight delay in bacteroid maturation. In contrast, cowpea nodules induced by the nolA mutant strains contained fewer infected cells and bacteroids were not found in a typical symbiosome structure. These results indicate that NolA is a transcriptional activator required for the expression of genes that play a role not only in the early stages of infection, but also during the later stages of bacteroid development and maintenance.
Mol Plant Microbe Interact 1996 Sep
PMID:Phenotypic characterization and regulation of the nolA gene of Bradyrhizobium japonicum. 881 78

SoxR protein is known to function both as a sensor and as a transcriptional activator for a superoxide response regulon in Escherichia coli. The activity of SoxR was tested by its ability to enable the transcription of its target gene, soxS, in vitro. The activity of the oxidized form was lost when its [2Fe-2S] clusters were reduced by dithionite under anaerobic conditions, and it was rapidly restored by autooxidation. This result is consistent with the hypothesis that induction of the regulon is effected by the univalent oxidation of the Fe-S centers of SoxR. In vivo, this oxidation may be caused by an alteration of the redox balance of electron chain intermediates that normally maintains soxR in an inactive, reduced state. Oxidized SoxR was about twice as effective as reduced SoxR in protecting the soxS operator from endonucleolytic cleavage. However, this difference could not account for a greater than 50-fold difference in their activities and therefore could not support a model in which oxidation activates SoxR by enabling it to bind to DNA. NADPH, ferredoxin, flavodoxin, or ferredoxin (flavodoxin):NADP+ reductase could not reduce SoxR directly in vitro at a measurable rate. The midpoint potential for SoxR was measured at -283 mV.
Proc Natl Acad Sci U S A 1996 Sep 17
PMID:SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form. 881 57

Bacteriophage T4 gene 45 protein, gp45, serves as the sliding clamp of viral DNA replication and as the activator of T4 late gene transcription. In the latter context, DNA tracking is an essential feature of the unique mechanism of action. T4 late promoters, which consist of a simple TATA box, TATAAATA, are recognized by the small sigma-family gene 55 protein, gp55, which binds to Escherichia coli RNA polymerase core. A direct and RNA polymerase-independent interaction of gp45 with gp55 has been demonstrated in two ways. (i) gp45 tracks along DNA; co-tracking of gp55 requires the previously documented DNA-loading process of gp45, and can be detected by photochemical crosslinking. (ii) The dynamics of DNA tracking by gp45 can be followed by footprinting; the catenated DNA-tracking state of gp45 is short-lived, but is stabilized by gp55. The ability of this topologically linked DNA-tracking transcriptional activator to interact directly with a promoter recognition protein suggests the existence of multiple pathways of promoter location, which are discussed.
EMBO J 1996 Sep 16
PMID:A direct interaction between a DNA-tracking protein and a promoter recognition protein: implications for searching DNA sequence. 889 Jan 76


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