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)

A group of four rhi (rhizosphere-expressed) genes from the symbiotic plasmid of Rhizobium leguminosarum biovar viciae has been characterized. Although mutation of the rhi genes does not normally affect nodulation, in the absence of the closely linked nodulation genes nodFEL, mutations in the rhi genes can influence the nodulation of the vetch Vicia hirsuta. The DNA sequence of the rhi gene region reveals four large open reading frames, three of them constituting an operon (rhiABC) transcribed convergently toward the fourth gene, rhiR. rhiABC are under the positive control of RhiR, the expression of which is repressed by flavonoids that normally induce nod gene expression. This repression, which requires the nodD gene product (the transcriptional activator of nod gene expression), may be due to a cis effect caused by a high level of NodD-dependent expression from the adjacent nodO promoter, which is transcribed divergently from rhiR. RhiR shows significant similarities to a subfamily of transcriptional regulators that includes the LuxR and UvrC-28K proteins. RhiA shows limited homology to a short domain of the lactose permease, LacY, close to a region thought to be involved in substrate binding. No strong homologies were found for the other rhi gene products. It appears that RhiA and RhiB are cytoplasmic, whereas RhiC is a periplasmic protein, since it has a typical N-terminal transit sequence and a rhiC-phoA protein fusion expresses alkaline phosphatase activity. The biochemical role of the rhi genes has not been established, but it appears that they may play a role in the plant-microbe interaction, possibly by allowing the bacteria to metabolize a plant-made metabolite.
 ...
PMID:Molecular characterization and regulation of the rhizosphere-expressed genes rhiABCR that can influence nodulation by Rhizobium leguminosarum biovar viciae. 159 18

The transposon TnphoA was used to generate fusions between phoA, the gene for alkaline phosphatase (PhoA), and genes encoding proteins that are secreted by Vibrio cholerae. One of the PhoA+ mutants isolated showed a dramatic reduction in its ability to colonize the intestines of suckling mice. This mutant no longer produced a 20.5-kDa protein (TcpA) that we show is the major subunit of a V. cholerae pilus. Amino-terminal sequence analysis of the TcpA pilus subunit showed that it shares amino acid homology with the pilins produced by several other pathogenic bacteria. The TcpA pilus was coordinately expressed with cholera toxin under various culture conditions, and this effect appeared to be dependent on the transcriptional activator encoded by the toxR gene. We conclude that the toxR gene plays a central role in the transcriptional regulation of multiple virulence genes of V. cholerae.
 ...
PMID:Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. 288 55

A gene fusion library of Vibrio cholerae classical strain O395 was generated by using a broad host range vector for delivery of the transposon TnphoA. The insertion library was screened for colonies expressing alkaline phosphatase-positive (PhoA+) fusion proteins on LB agar at 30 degrees C in the presence of 0.2% glucose. Over 600 PhoA+ strains were isolated and then tested for regulation of their gene fusions in broth media that permitted high or low expression of cholera toxin. This strategy resulted in the isolation of 60 TnphoA (Tn5 IS50L::phoA) fusions to genes encoding secreted proteins that are apparently coordinately regulated with cholera toxin. Introduction of a toxR null mutation into 10 of these fusion strains confirmed that these TnphoA gene fusions are controlled either directly or indirectly by the cholera toxin transcriptional activator encoded by toxR. A combination of Southern and immunoblot analysis identified 17 distinct ToxR-regulated genes in V. cholerae O395. Many of these insertions were located in one of the two cholera toxin operon copies of strain O395, as well as a large gene cluster involved in the biogenesis of the toxin-coregulated pilus colonization factor. In addition, insertions were identified in genes that had no effect on either cholera toxin or toxin-coregulated pilus expression. Several of these insertions were localized to a cluster of four genes, the disruption of any of which by TnphoA reduced the ability of strain O395 to colonize the intestines of suckling mice. The product encoded by this second gene cluster was named accessory colonization factor to describe its possible role in cholera pathogenesis. These studies reinforce the contribution of ToxR-regulated genes to the virulence properties of V. cholerae. This report also demonstrates a new approach for the identification of bacterial virulence factors, based on the characterization of genes that are regulated by the same environmental signals that control the expression of a known virulence factor.
 ...
PMID:Characterization of the Vibrio cholerae ToxR regulon: identification of novel genes involved in intestinal colonization. 290 9

The toxR gene encodes a transcriptional activator controlling cholera toxin, pilus, and outer-membrane protein expression in V. cholerae. Nucleotide sequence and mutational analysis has identified the toxR gene product as a 32,527 dalton protein. Hydropathicity analysis of the derived amino acid sequence of ToxR predicts a transmembrane structure. The properties of hybrid proteins composed of N-terminal fragments of ToxR fused to the periplasmic enzyme alkaline phosphatase provide additional evidence for the transmembrane topology of the ToxR protein. These fusion proteins also allowed the localization of the transcriptional activation and DNA binding domains of the ToxR protein to its cytoplasmically located N-terminal portion. DNA binding assays and a deletion analysis of the cholera toxin promoter support a model for transcriptional activation that involves ToxR binding to a tandemly repeated 7 bp DNA sequence 56 bp upstream of the transcriptional start point.
 ...
PMID:Cholera toxin transcriptional activator toxR is a transmembrane DNA binding protein. 380 95

The phoE promoter region in Escherichia coli contains a -10 region, typical of sigma 70-dependent promoters and, instead of a normal -35 region, a so-called pho box, to which the transcriptional activator phospho-PhoB binds under low phosphate conditions. A second pho box is present upstream of the first one and is required for full expression of phoE during phosphate starvation. To determine whether the lack of expression under high phosphate conditions is due solely to the absence of a genuine -35 box, the -10 region was further optimized towards the consensus -10 sequence and promoter activity was measured using alkaline phosphatase as a reporter. The mutations resulted in a drastic increment in the basal level of expression under high phosphate conditions, indicating that the deviations from consensus in the -10 region also play a role in determining the poor expression of the wild-type promoter under these conditions. The expression under high phosphate conditions was partly dependent on the presence of the phoB gene, showing that a small amount of active PhoB must be present under these circumstances. During phosphate starvation, the activity of the mutant promoters was further induced. The upstream pho box was not required for full expression from the mutant promoters under these conditions. Apparently, the wild-type phoE promoter is carefully balanced by deviations from the optimal Pribnow box sequence that reduce expression under high phosphate conditions and by the presence of several copies of the pho box, which enhance expression under phosphate starvation.
 ...
PMID:Effect of mutations in the -10 region of the phoE promoter in Escherichia coli on regulation of gene expression. 781 30

GATA-1 is a cys-2/cys-2 zinc finger transcriptional activator that is required for erythrocyte development in chimeric mice and contributes to the expression of all erythroid genes studied to date, including the erythropoietin receptor, glycophorin B, and porphobilinogen deaminase genes. Transactivation by GATA-1 is mediated by either an amino-terminal acidic domain, R1, or an independent adjacent domain, R2, and may involve the coordinate action of cofactors (NF-E2, EKLF, and Sp1) which bind adjacent cis-elements. To directly assess mechanisms of transactivation, we have developed an efficient cell-free transcription system using recombinant human GATA-1 (rhGATA-1) expressed in SF9 cells. Levels of baculoviral expression of GATA-1 were > or = 200-fold higher than endogenous levels in erythroid K562 cells. Factors from each source were essentially equivalent in molecular weight and DNA binding properties, and highly similar in phosphotryptic peptide composition. Notably, DNA binding was inhibited following treatment with alkaline phosphatase. In both SF9 and K562 cells, GATA-1 occurred largely as heterogeneous multimers, thus complicating its isolation by standard procedures. However, significant purification of this factor (> or = 100-fold; > or = 75% purity) was accomplished via DNA affinity chromatography. In cell-free assays, this rhGATA-1 was shown to be remarkably active in transactivating model erythroid promoters. This work establishes an efficient in vitro system for direct analyses of mechanisms, cofactors, and functional domains of GATA-1 which regulate transcription at defined proximal promoters.
 ...
PMID:In vitro transcription of erythroid promoters using baculoviral-expressed human GATA-1: purification, physicochemistry, and activities. 785 29

The ftsH gene encodes an ATP- and Zn(2+)-dependent metalloprotease with a molecular mass of about 70 kDa. It was first identified in Escherichia coli where it is also designated hflB, tolZ or mrsC, and seems to be present in most if not all bacteria. The FtsH protein is anchored to the cytoplasmic membrane via two transmembrane regions in such a way that the very short amino- and the long carboxy-termini are exposed into the cytoplasm. FtsH is member of the AAA family (ATPases associated with a variety of cellular activities) which are characterized by a module of about 200 amino acid residues in length containing an ATP-binding site. In Escherichia coli, FtsH forms a complex with a pair of periplasmically exposed membrane proteins, HflK and HflC. The E. coli enzyme is required for proteolytic degradation of some unstable proteins that include both soluble regulatory proteins such as sigma 32 (heat-shock sigma factor) and phage lambda CII (transcriptional activator), and membrane proteins including uncomplexed forms of SecY (forms the translocon together with SecE and SecG) and the a subunit of the F0 complex of the H(+)-ATPase. Its activity can be modulated by the HflKC proteins, by another membrane protein designated YccA which can transiently associate with both the FtsH and the HflKC proteins, or by small peptides such as CIII encoded by phage lambda (involved in lysogenization) or SpoVM (needed for sporulation) encoded by Bacillus subtilis. Besides being a protease, there is circumstantial evidence that FtsH also acts as a molecular chaperone. It influences protein assembly in and through the cytoplasmic membrane and associates with denatured alkaline phosphatase without degrading it. Therefore, FtsH may serve to maintain quality control of some cytoplasmic and membrane proteins. Such ATP-dependent proteases with intrinsic chaperone activity have been designated charonins.
 ...
PMID:FtsH--a single-chain charonin? 1007 51

Under physiological conditions, the Escherichia coli cytoplasm is maintained in a reduced state that strongly disfavors the formation of stable disulfide bonds in proteins. However, mutants in which the reduction of both thioredoxins and glutathione is impaired (trxB gor mutants) accumulate oxidized, enzymatically active alkaline phosphatase in the cytoplasm. These mutants grow very poorly in the absence of an exogenous reductant and accumulate extragenic suppressors at a high frequency. One such suppressor strain, FA113, grows almost as rapidly as the wild type in the absence of reductant, exhibits slightly faster kinetics of disulfide bond formation, and has fully induced activity of the transcriptional activator, OxyR. FA113 gave substantially higher yields of properly oxidized proteins compared with wild-type or trxB mutant strains. For polypeptides with very complex patterns of disulfide bonds, such as vtPA and the full-length tPA, the amount of active protein was further enhanced up to 15-fold by co-expression of TrxA (thioredoxin 1) mutants with different redox potentials, or 20-fold by the protein disulfide isomerase, DsbC. Remarkably, higher yields of oxidized, biologically active proteins were obtained by expression in the cytoplasm of E. coli FA113 compared with what could be achieved via secretion into the periplasm of a wild-type strain, even under optimized conditions. These results demonstrate that the cytoplasm can be rendered sufficiently oxidizing to allow efficient formation of native disulfide bonds without compromising cell viability.
 ...
PMID:Efficient folding of proteins with multiple disulfide bonds in the Escherichia coli cytoplasm. 1057 Jan 36

Mimosine is a toxin present in the tree-legume leucaena (Leucaena leucocephala), including its root nodules and the root exudates. The leucaena-nodulating Rhizobium sp. strain TAL1145 degrades mimosine (Mid(+)) and utilizes it as a source of carbon and nitrogen. Twelve TAL1145 mutants defective in mimosine degradation (Mid(-)) were made through Tn3Hogus, TnphoA or kanamycin-resistance-cassette insertions. A 5.0 kb PstI fragment of TAL1145, subcloned from a cosmid clone containing mid genes for mimosine degradation, complemented most of the Mid(-) mutants. Sequencing this fragment and the adjacent 0.9 kb PstI fragment identified five genes, midA, midB, midC, midD and midR, of which the first three genes encode ABC transporter proteins involved in mimosine uptake, while midD encodes an aminotransferase required for degrading mimosine into 3-hydroxy-4-pyridone, and midR is a regulatory gene encoding a LysR-type transcriptional activator. The location of MidA in the periplasm was shown by making two midA : : phoA fusions, which made active alkaline phosphatase in the periplasm. The various mid : : gus and midA : : phoA fusions were inducible by mimosine, and a midD : : gus fusion mutant showed beta-glucuronidase activity in the leucaena nodules, indicating that midD is expressed in the nodules. Similarly, a midA : : phoA fusion expressed alkaline phosphatase activity in the leucaena nodules, indicating that mimosine induces midA transcription in the bacteroids. mid genes are specific for the Mid(+) strains of leucaena Rhizobium and are absent in strains of other Rhizobium, Sinorhizobium and Bradyrhizobium spp.
 ...
PMID:The mid genes of Rhizobium sp strain TAL1145 are required for degradation of mimosine into 3-hydroxy-4-pyridone and are inducible by mimosine. 1262 15

Runx2, a transcriptional activator downstream of bone morphogenetic protein (BMP) signaling, is essential to osteoblastic differentiation and bone formation and maintenance. BMPs activate complex signaling networks, utilizing numerous signaling molecules and transcription factors to induce expression of osteoblastic markers in mesenchymal cell types. However, the role of Runx2 in this process, particularly in an environment independent of the other regulatory elements modulated by BMPs, remains poorly understood. In the present study, we used retroviral gene delivery to examine the effects of sustained Runx2 expression in primary myoblasts. Runx2 inhibited myogenesis, as demonstrated by suppression of MyoD and myogenin mRNA levels and reduced myotube formation. Additionally, Runx2-stimulated osteogenesis including osteoblastic gene expression, alkaline phosphatase activity, and biological mineral deposition. Notably, these osteogenic markers were induced to significantly greater levels than those observed in BMP-2-treated controls. These results demonstrate that direct exogenous expression of the Runx2 transcription factor, only one of numerous downstream targets of BMP signaling, is sufficient to induce transdifferentiation of myogenic cells into a mineralizing osteogenic lineage. This work underscores the potency of Runx2 as a regulator of osteogenesis and cell differentiation and provides new insights into the plasticity of committed mesenchymal cells.
 ...
PMID:Runx2/Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype. 1547 5


1 2 Next >>