Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor (TF) is the primary initiator of the coagulation protease cascades. This cell surface glycoprotein is the receptor and essential cofactor for the serine protease factor VIIa. TF is constitutively expressed in some extravascular cell types and is transiently induced in monocytes, endothelial cells, and fibroblasts. Inducible expression is implicated in cellular immune responses, inflammation, and intravascular coagulation. Transcriptional regulation of the TF promoter was analyzed in COS-7 cells under conditions of (i) high-level expression and (ii) serum induction. The region comprising nucleotides -209 to +121 (relative to the transcription start site) supports high-level transcriptional activity and can be divided into two distinct regions: a region (-111 to +121) that exhibited low promoter activity and a region (-209 to -112) that enhanced transcriptional activity to a high level. The role of further upstream sequences is still to be established, although two consensus binding sites for the transcriptional activator protein AP-1 did enhance low-level promoter activity. In serum-starved COS-7 cells TF expression was transiently increased 20-fold by serum. All transcriptionally active constructs were responsive to serum, indicating the presence of at least one serum response element, whose function was retained in the immediate 5' aspect of the gene, at -111 to +14. Based on this functional map, we propose that the elaborate pattern of TF expression by cells results from a relatively complex promoter.
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PMID:Functional analysis of the human tissue factor promoter and induction by serum. 231 17

AdpA is a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus, activating a number of genes required for secondary metabolism and morphological differentiation. Of the five chymotrypsin-type serine protease genes, sprA, sprB, and sprD were transcribed in response to AdpA, showing that these protease genes are members of the AdpA regulon. These proteases were predicted to play the same physiological role, since these protease genes were transcribed in a similar time course during growth and the matured enzymes showed high end-to-end similarity to one another. AdpA bound two sites upstream of the sprA promoter approximately at positions -375 and -50 with respect to the transcriptional start point of sprA. Mutational analysis of the AdpA-binding sites showed that both AdpA-binding sites were essential for transcriptional activation. AdpA bound a single site at position -50 in front of the sprB promoter and greatly enhanced the transcription of sprB. The AdpA-binding site at position -40 was essential for transcription of sprD, although there was an additional AdpA-binding site at position -180. Most chymotrypsin activity excreted by S. griseus was attributed to SprA and SprB, because mutant deltasprAB, having a deletion in both sprA and sprB, lost almost all chymotrypsin activity, as did mutant deltaadpA. Even the double mutant deltasprAB and triple mutant deltasprABD grew normally and developed aerial hyphae and spores over the same time course as the wild-type strain.
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PMID:Three chymotrypsin genes are members of the AdpA regulon in the A-factor regulatory cascade in Streptomyces griseus. 1615 67

XprG, a putative p53-like transcriptional activator, regulates production of extracellular proteases in response to nutrient limitation and may also have a role in programmed cell death. To identify genes that may be involved in the XprG regulatory pathway, xprG2 revertants were isolated and shown to carry mutations in genes which we have named sogA-C (suppressors of xprG). The translocation breakpoint in the sogA1 mutant was localized to a homolog of Saccharomyces cerevisiae VPS5 and mapping data indicated that sogB was tightly linked to a VPS17 homolog. Complementation of the sogA1 and sogB1 mutations and identification of nonsense mutations in the sogA2 and sogB1 alleles confirmed the identification. Vps17p and Vps5p are part of a complex involved in sorting of vacuolar proteins in yeast and regulation of cell-surface receptors in mammals. Protease zymograms indicate that mutations in sogA-C permit secretion of intracellular proteases, as in S. cerevisiae vps5 and vps17 mutants. In contrast to S. cerevisiae, the production of intracellular protease was much higher in the mutants. Analysis of serine protease gene expression suggests that an XprG-independent mechanism for regulation of extracellular protease gene expression in response to carbon starvation exists and is activated in the pseudorevertants.
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PMID:Mutations in genes encoding sorting nexins alter production of intracellular and extracellular proteases in Aspergillus nidulans. 1920 78

Enteroaggregative Escherichia coli (EAEC) is increasingly being recognized as a cause of diarrheal disease in diverse populations. No small animal model is currently available to study this pathogen. We report here that conventional mice orally inoculated with prototype EAEC strain 042 generally became colonized, though the abundance of organisms cultured from their stool varied substantially among individual animals. In contrast, mice whose water contained 5 g/liter streptomycin consistently became colonized at high levels (ca. 10(8) CFU/g of stool). Neither conventional nor streptomycin-treated mice developed clinical signs or histopathologic abnormalities. Using specific mutants in competition with the wild-type strain, we evaluated the contribution of several putative EAEC virulence factors to colonization of streptomycin-treated mice. Our data suggest that the dispersin surface protein and Pic, a serine protease autotransporter secreted by EAEC and Shigella flexneri, promote colonization of the mouse. In contrast, we found no role for the aggregative adherence fimbriae, the transcriptional activator AggR, or the surface factor termed Air (enteroaggregative immunoglobulin repeat protein). To study Pic further, we constructed a single nucleotide mutation in strain 042 which altered only the Pic catalytic serine (strain 042PicS258A). Fractionation of the tissue at 24 h and 3 days demonstrated an approximate 3-log(10) difference between 042 and 042PicS258A in the lumen and mucus layer and adherent to tissue. Strains 042 and 042PicS258A adhered similarly to mouse tissue ex vivo. While no growth differences were observed in a continuous-flow anaerobic intestinal simulator system, the wild-type strain exhibited a growth advantage over 042PicS258A in a culture of cecal mucus and in cecal contents in vitro; this difference was manifest only after 6 h of growth. Moreover, enhanced growth of the wild type was observed in comparison with that of the mutant in minimal medium containing mucin but not in the absence of mucin. The data suggest a novel metabolic role for the Pic mucinase in EAEC colonization.
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PMID:The Pic protease of enteroaggregative Escherichia coli promotes intestinal colonization and growth in the presence of mucin. 1934 28