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)

Proper growth and development of multicellular organisms requires precise regulation of developmental genes. One aspect of this regulation is at the level of transcription from the gene promoters. As an initial approach to understanding the regulation of the Pax-6 gene, which plays an important role in eye development and perhaps in other developmental processes, we characterized a promoter region of the quail Pax-6 (Pax-QNR) gene. Sequence analysis of the 5' flanking region revealed a TATA-like box and a CAAT box as well as several putative cis-regulatory elements. A 1.5-kilobase pair fragment, containing 1386 base pairs of 5' flanking sequence, the first exon, and a portion of the first intron, was able to efficiently promote expression of the bacterial CAT gene in quail neuroretina cells. Cotransfection of the Pax-QNR promoter with a vector expressing the 46 kilodalton Pax-QNR protein resulted in an increase in Pax-QNR promoter activity. By electrophoretic migration shift assay and immunoselection experiments, we showed that the Pax-QNR protein can interact directly with the Pax-QNR promoter. By footprinting experiments, we identified the binding sites for the Pax-QNR protein within the promoter region. These results show that Pax-QNR encodes a transcriptional activator and that it potentially trans-activates its own promoter.
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PMID:Quail Pax-6 (Pax-QNR) encodes a transcription factor able to bind and trans-activate its own promoter. 811 18

Pseudomonas aeruginosa K372 is deficient in the production of both the 75-kDa ferripyochelin receptor protein and pyochelin. A 1.8-kb EcoRI-SalI fragment which restored production of both the receptor protein and pyochelin was cloned. Nucleotide sequencing of the fragment revealed an open reading frame of 888 bp, designated pchR (pyochelin), capable of encoding a 296-amino-acid protein of a 32,339-Da molecular mass. By using a phage T7-based expression system, a protein of ca. 32 kDa was produced off the 1.8-kb fragment, confirming that this open reading frame was indeed expressed. A region exhibiting homology to the consensus Fur-binding site of Escherichia coli was identified upstream of the pchR coding region overlapping a putative promoter. In addition, the C-terminal 80 amino acid residues of PchR showed approximately 50% homology (identity, 31%; conserved changes, 19%) to the carboxy terminus of AraC, a known transcriptional activator of gene expression in E. coli, Salmonella typhimurium, Citrobacter freundii, and Erwinia chrysanthemi. Within the C-terminal region of PchR, AraC, and a number of other members of the AraC family of transcriptional activators, there exists a highly conserved 17-residue domain where, in fact, two residues are strictly maintained and two others exhibit only conserved changes, suggesting a common functional significance to this region in all of these proteins. These data are consistent with a role for PchR as a transcriptional activator of pyochelin and ferripyochelin receptor synthesis in P. aeruginosa. In agreement with this, a PchR mutant obtained by in vitro mutagenesis and gene replacement was deficient in production of the ferripyochelin receptor and pyochelin.
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PMID:Cloning and sequence analysis of a gene (pchR) encoding an AraC family activator of pyochelin and ferripyochelin receptor synthesis in Pseudomonas aeruginosa. 839 86

A 1,026-bp open reading frame sharing significant similarity with queA, which encodes a predicted S-adenosylmethionine:tRNA ribosyltransferase-isomerase responsible for queosine modification of tRNAs, was found immediately 5' of the gene for the transcriptional activator (ArcR) of the arginine deiminase system (ADS) operon of Streptococcus gordonii. The role of QueA in bacterial physiology is enigmatic, but loss of QueA has been shown to compromise stationary-phase survival or virulence in certain enteric bacteria. Interestingly, S. gordonii appears to be unique among ADS-positive bacteria in the linkage of queA with the ADS genes. A putative sigma(70) promoter (p(queA); TTGCCA-N(21)-TATAAT) was mapped 5' of queA by primer extension, and queA and arcR were shown to be cotranscribed. The expression from p(queA) was found to be constitutive under all conditions tested, but the expression of p(arcA), which drives the expression of the arc structural genes, was enhanced in stationary phase and could be induced by low pH and arginine. QueA and CcpA acted repressively on arc transcription, but neither QueA-deficient strains nor CcpA-deficient strains showed significant differences in arginine deiminase enzyme activities compared with the wild-type strain. The growth rate of a QueA-deficient strain did not differ significantly from that of the parental strain, but the QueA-deficient strain did not compete well with the wild-type during serial passage. In addition to the finding that ADS expression can be regulated separately by growth phase and pH, a significant linkage between the ADS, translational efficiency modulated by QueA, and post-exponential-phase survival of S. gordonii was found.
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PMID:Environmental and growth phase regulation of the Streptococcus gordonii arginine deiminase genes. 1855 85

Pro-apoptotic Bax is essential for RGC (retinal ganglion cell) death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2J(Bax+/-) mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax(-/-) mice), but 129B6(Bax+/-) mice exhibited significant cell loss (similar to wild-type mice). The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T(129B6) to C(DBA/2J)) at position -515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53(-/-) cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA-protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.
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PMID:A single nucleotide polymorphism in the Bax gene promoter affects transcription and influences retinal ganglion cell death. 2036 Sep 47