Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

This review describes a range of pH responses. Some are only induced if relevant DNA is brought to an appropriately supercoiled configuration by DNA gyrase and bent by the action of, for example, integration host factor (IHF). Bending may allow transcription by bringing activators into juxtaposition with RNA polymerase, which is CysB-associated in several of the responses. Control of arginine decarboxylase (AdiA) synthesis at acid pH is of the above type, with dependence on the presence of gyrase, H-NS, IHF and CysB; acid induction of LysU has similar requirements but also needs Lrp; lysine decarboxylase (CadA) formation at acid pH is controlled quite differently, needing the CadC activator and interaction of lysine/lysine permease; H-NS probably reverses induction by CadC. The Hyd components of formic hydrogenlyase are induced by acid under anaerobiosis; a transcriptional activator is involved and Fur may also function in regulation. Acid tolerance induced at low pH in log-phase cells needs CysB and PhoE but not DNA gyrase; tolerance is reduced by NaCl but not affected by Fe3+, Fe2+, glucose/cAMP or by lrp, him, fur, hns or nhaA/B lesions. Alkali tolerance (habituation), induced at pH0 8.5-9.0, probably involves DNA supercoiling and bending; the induction process needs IHF, CysB, PhoE, NhaA, TonB and Fur and is glucose-repressed; tolerance may result from Na+ efflux catalysed by the NhaA antiporter, which is induced at pH0 9.0. Alkali sensitivity induced at pH0 5.5 also requires gyrase, IHF and CysB, but H-NS, Lrp, NhaA and OmpC are also needed and induction is abolished by NaCl. Salt-induced acid sensitivity results from PhoE formation and is blocked by glucose (reversed by cAMP), FeCl3 and hns and relA lesions, the effect of relA being envZ-suppressed. Acid sensitivity induction (ASI) at pH0 9.0 needs H-NS, is inhibited by FeCl3 and amiloride, and is associated with alkyl hydroperoxide reductase synthesis. Leucine-induced acid sensitivity needs gyrase, CysB, H-NS, Fur, OmpA and RelA, is inhibited by Fe3+, Fe2+, tetracycline, glucose and nalidixic acid, but not by chloramphenicol; increased outer membrane proton passage may result from OmpA modification.
...
PMID:Regulatory components, including integration host factor, CysB and H-NS, that influence pH responses in Escherichia coli. 917 36

Starvation for sulfate results in increased synthesis of several proteins in Escherichia coli. Among these Ssi (sulfate starvation-induced) proteins are the products of the tauABCD genes, which are required for utilization of taurine as sulfur source for growth. In this study, the role of the cbl gene in expression of tauABCD and other ssi genes was investigated. The protein encoded by cbl shows high sequence similarity to CysB, the LysR-type transcriptional activator of the genes involved in cysteine biosynthesis. Strain EC2541, which contains an internal deletion in cbl, was unable to utilize taurine and other aliphatic sulfonates as sulfur sources. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that many of the Ssi proteins were not synthesized in EC2541. Expression of a translational tauD'-'lacZ fusion required the presence of both cbl and cysB. The interactions of CysB and Cbl with the promoter region of tauABCD were studied by using gel mobility shift experiments and DNase I footprinting. CysB occupied multiple binding sites, whereas Cbl occupied only one site from 112 to 68 bp upstream of the transcription start site. Acetylserine, the inducer of transcription of CysB-regulated genes, stimulated binding of CysB but not of Cbl. Sulfate had no effect on binding of both proteins to the tauABCD promoter region. These results indicate that Cbl is a transcription factor for genes required for sulfonate-sulfur utilization and maybe for other genes whose expression is induced by sulfate starvation.
...
PMID:Involvement of CysB and Cbl regulatory proteins in expression of the tauABCD operon and other sulfate starvation-inducible genes in Escherichia coli. 940 Oct 24

Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory flavoprotein that modulates the activity of the transcriptional activator NIFA in response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in vitro. Limited proteolysis of NIFL indicates that it comprises a relatively stable N-terminal domain and a C-terminal domain that is protected from trypsin digestion in the presence of adenosine nucleotides. ATP protects the protein from cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus, whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130 microM for ATP and 16 microM for ADP. The purified N-terminal domain has an identical UV/visible absorption spectrum to the wild-type protein and is reduced by sodium dithionite, demonstrating that it is a flavin-binding domain. The isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment containing 160 residues of the C-terminal region, including the nucleotide-binding sites, is also not competent to inhibit NIFA. Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response. However, this truncated protein remains competent to inhibit NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are therefore separable and are discrete functions of the protein.
...
PMID:The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains. 959 6

Yeast cells deficient in the transcriptional activator Imp2p are viable, but display marked hypersensitivity to a variety of oxidative agents. We now report that imp2 null mutants are also extremely sensitive to elevated levels of the monovalent ions, Na+ and Li+, as well as to the divalent ions Ca2+, Mn2+, Zn2+, and Cu2+, but not to Cd2+, Mg2+, Co2+, Ni2+, and Fe2+, as compared to the parent strain. We next searched for multicopy suppressor genes that would allow the imp2Delta mutant to grow under high salt conditions. Two genes that independently restored normal salt-resistance to the imp2Delta mutant, ENA1 and HAL3, were isolated. ENA1 encodes a P-type ion pump involved in monovalent ion efflux from the cell, while HAL3 encodes a protein required for activating the expression of Ena1p. Neither ENA1 nor HAL3 gene expression was positively regulated by Imp2p. Moreover, the imp2 ena1 double mutant was exquisitely sensitive to Na+/Li+ cations, as compared to either single mutant, implying that Imp2p mediates Na+/Li+ cation homeostasis independently of Ena1p.
...
PMID:The transcriptional activator Imp2p maintains ion homeostasis in Saccharomyces cerevisiae. 961 Dec

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a lymphotropic virus strongly linked to the development of KS, an endothelial cell neoplasm frequent in persons with AIDS. Reactivation from latency in B cells is thought to be an important antecedent to viral spread to endothelial cells during KS pathogenesis. Earlier experiments have posited a role for the transcriptional activator encoded by KSHV open reading frame 50 (ORF50) in such reactivation, since ectopic overexpression of this protein induces reactivation in latently infected B cells. Here we have explored several aspects of the expression, structure, and function of this protein bearing on this role. The ORF50 gene is expressed very early in lytic reactivation, before several other genes implicated as candidate regulatory genes in related viruses, and its expression can upregulate their promoters in transient assays. The protein is extensively phosphorylated in vivo and bears numerous sites for phosphorylation by protein kinase C, activators of which are potent stimulators of lytic induction. The C terminus of the ORF50 protein contains a domain that can strongly activate transcription when targeted to DNA; deletion of this domain generates an allele that expresses a truncated protein which retains the ability to form multimers with full-length ORF50 and functions as a dominant-negative protein. Expression of this allele in latently infected cells ablates spontaneous reactivation from latency and strikingly suppresses viral replication induced by multiple stimuli, including phorbol ester, ionomycin, and sodium butyrate. These results indicate that the ORF50 gene product plays an essential role in KSHV lytic replication and are consistent with its action as a putative molecular switch controlling the induction of virus from latency.
...
PMID:Transcriptional activation by the product of open reading frame 50 of Kaposi's sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. 1051 43

Quorum sensing (QS) governs the production of virulence factors and the architecture and sodium dodecyl sulphate (SDS) resistance of biofilm-grown Pseudomonas aeruginosa. P. aeruginosa QS requires two transcriptional activator proteins known as LasR and RhlR and their cognate autoinducers PAI-1 (N-(3-oxododecanoyl)-L-homoserine lactone) and PAI-2 (N-butyryl-L-homoserine lactone) respectively. This study provides evidence of QS control of genes essential for relieving oxidative stress. Mutants devoid of one or both autoinducers were more sensitive to hydrogen peroxide and phenazine methosulphate, and some PAI mutant strains also demonstrated decreased expression of two superoxide dismutases (SODs), Mn-SOD and Fe-SOD, and the major catalase, KatA. The expression of sodA (encoding Mn-SOD) was particularly dependent on PAI-1, whereas the influence of autoinducers on Fe-SOD and KatA levels was also apparent but not to the degree observed with Mn-SOD. beta-Galactosidase reporter fusion results were in agreement with these findings. Also, the addition of both PAIs to suspensions of the PAI-1/2-deficient double mutant partially restored KatA activity, while the addition of PAI-1 only was sufficient for full restoration of Mn-SOD activity. In biofilm studies, catalase activity in wild-type bacteria was significantly reduced relative to planktonic bacteria; catalase activity in the PAI mutants was reduced even further and consistent with relative differences observed between each strain grown planktonically. While wild-type and mutant biofilms contained less catalase activity, they were more resistant to hydrogen peroxide treatment than their respective planktonic counterparts. Also, while catalase was implicated as an important factor in biofilm resistance to hydrogen peroxide insult, other unknown factors seemed potentially important, as PAI mutant biofilm sensitivity appeared not to be incrementally correlated to catalase levels.
...
PMID:Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. 1059 32

The transmembrane regulatory protein ToxR is required for expression of virulence factors in the human diarrheal pathogen Vibrio cholerae, including cholera toxin (CT) and the toxin coregulated pilus (TCP). ToxR is necessary for transcription of the gene encoding a second regulatory protein, ToxT, which is the direct transcriptional activator of CT and TCP genes. However, ToxR, independent of ToxT, directly activates and represses transcription of the outer membrane porins OmpU and OmpT, respectively. The genes encoding TCP and CT (and including ToxT) lie on horizontally acquired genetic elements, while the toxR, ompU, and ompT genes are apparently in the ancestral Vibrio chromosome. The contribution of ToxR-dependent modulation of outer membrane porins to cholera pathogenesis has remained unknown. We demonstrate that ToxR mediates enhanced bile resistance in a ToxT-independent manner. In both classical and El Tor biotypes of V. cholerae, a toxR mutant strain has a reduced minimum bactericidal concentration (MBC) of bile, the bile component deoxycholate (DC), and the anionic detergent sodium dodecyl sulfate (SDS) compared to both wild-type and toxT mutant strains. Classical and El Tor toxR mutant strains also exhibit reduced growth rates at subinhibitory concentrations of DC and SDS. Growth of either V. cholerae biotype in subinhibitory concentrations of bile or DC induces increased ToxR-dependent production of a major 38-kDa outer membrane protein, which was confirmed to be OmpU by Western blot. Measurement of transcription of a ompUp-lacZ fusion in both biotypes reveals stimulation (about two- to threefold) of ToxR-dependent ompU transcription by the presence of bile or DC, suggesting that ToxR may respond to the presence of bile. The toxR mutant strains of three additional human intestinal pathogenic Vibrio species, V. mimicus, V. fluvialis, and V. parahaemolyticus, display lower MBCs of bile, DC, and SDS and have altered outer membrane protein profiles compared to the parental wild-type strains. Our results demonstrate a conserved role for ToxR in the modulation of outer membrane proteins and bile resistance of pathogenic Vibrio species and suggest that these ToxR-dependent outer membrane proteins may mediate enhanced resistance to bile. We speculate that ToxR-mediated bile resistance was an early step in the evolution of V. cholerae as an intestinal pathogen.
...
PMID:The virulence regulatory protein ToxR mediates enhanced bile resistance in Vibrio cholerae and other pathogenic Vibrio species. 1067 65

Retroviruses are currently the most widely used vectors in clinical trials for gene therapy. These vectors are, however, limited by low titres partly due to the restrictive nature of monolayer cell culture. We have developed a stable suspension producer cell line derived from human lymphoblastoid cells (WIL-2) by electroporating these cells with the necessary trans components required for production of defective retrovirus particles which encode a nuclear localising beta-galactosidase gene. We show that this anchorage-independent cell line generates viruses at a titre of 7 x 10(5) iu/ml on NIH3T3 indicator cells which remains constant after at least 2 months in culture. The producer cells can be cultured at a density of 6 x 10(6) cells/ml with consistent virus titre production. WIL-2 can also be grown as single cells by rotation culture while maintaining virus production. By treating the cells with the transcriptional activator sodium butyrate titres above 1 x 10(6) i.u./ml are achieved. Concentrating viral supernatants by ultrafiltration can further increase virus titre to 5 x 10(8) i.u./ml. Even at these high titres no replication-competent virus was detected. Virus titre fell only slightly when cells were placed in serum-free media before harvest. The generation of this novel cell line provides proof-of-principle that large-scale production of retroviral vectors in serum-free growth conditions can be safely generated for use in gene therapy.
...
PMID:A novel human suspension culture packaging cell line for production of high-titre retroviral vectors. 1140 64

TonEBP is a transcriptional activator that is expressed throughout development in many tissues and cell types. In the kidney medulla, TonEBP appears to be an important local regulator of differentiation by virtue of stimulating several genes. To study the function of TonEBP, two small interfering RNA (siRNA) duplexes were developed that reduced TonEBP expression effectively via RNA interference. The silencing lasted only 3 d after introduction of the TonEBP-siRNA's. As expected, TonEBP-driven reporter gene expression and expression of the sodium/myo-inositol cotransproter (SMIT), aldose reductase (AR) and heat shock protein 70 (HSP70) mRNA were significantly decreased in cells where TonEBP expression was silenced. These data provide direct evidence that the SMIT, AR, and HSP70 genes are targets of TonEBP, although the potential role of other proteins, such as accessory proteins, cannot be excluded. The TonEBP-siRNA is an effective tool that should prove useful in the investigation of loss-of-function relationship in cells.
...
PMID:Silencing of TonEBP/NFAT5 transcriptional activator by RNA interference. 1253 27

Expression of the pspABCDE operon of Escherichia coli is induced upon infection by filamentous phage and by many other stress conditions, including defects in protein export. Expression of the operon requires the alternative sigma factor sigma54 and the transcriptional activator PspF. In addition, PspA plays a negative regulatory role, and the integral-membrane proteins PspB and PspC play a positive one. In this study, we investigated whether the suggested protein-protein interactions implicated in this complex regulatory network can indeed be demonstrated. Antisera were raised against PspB, PspC, and PspD, which revealed, in Western blotting experiments, that PspC forms stable sodium dodecyl sulfate-resistant dimers and that the hypothetical pspD gene is indeed expressed in vivo. Fractionation experiments showed that PspD localizes as a peripherally bound inner membrane protein. Cross-linking studies with intact cells revealed specific interactions of PspA with PspB and PspC, but not with PspD. Furthermore, affinity-chromatography suggested that PspB could bind PspA only in the presence of PspC. These data indicate that regulation of the psp operon is mediated via protein-protein interactions.
...
PMID:Interactions between phage-shock proteins in Escherichia coli. 1256 86


<< Previous 1 2 3 4 Next >>

---