Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EGR-1 gene is an immediate early response gene encoding a zinc finger DNA-binding protein. The present studies have examined the regulation of EGR-1 gene expression in human U-937 monocytic leukemia cells treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). The results demonstrate that GM-CSF rapidly and transiently increases EGR-1 gene expression in U-937 cells. Similar findings were obtained in GM-CSF-treated human monocytes. We also show that the regulation of EGR-1 expression by GM-CSF is a pertussis toxin-sensitive event. The results of nuclear run-on assays further demonstrate that the EGR-1 gene is constitutively transcribed in untreated U-937 cells and that GM-CSF has little effect on this rate of transcription. Inhibition of protein synthesis with cycloheximide also had no detectable effect on EGR-1 gene transcription but was associated with superinduction of EGR-1 mRNA levels in GM-CSF-treated cells. Moreover, the half-life of GM-CSF-induced EGR-1 transcripts was prolonged from 33 to 70 min following inhibition of protein synthesis. Taken together, the results indicate that GM-CSF activates signaling pathways which regulate EGR-1 gene expression through a pertussis toxin-sensitive G protein and that these events increase EGR-1 mRNA levels by a posttranscriptional mechanism. This GM-CSF-dependent regulation of EGR-1 expression may provide a mechanism for transducing signals to the nucleus that are involved in the control of gene transcription.
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PMID:Posttranscriptional regulation of the zinc finger-encoding EGR-1 gene by granulocyte-macrophage colony-stimulating factor in human U-937 monocytic leukemia cells: involvement of a pertussis toxin-sensitive G protein. 206 96

A novel nonhemolytic phase variant of Bordetella pertussis was characterized. This strain is strongly impaired in the transcription of the pertussis and adenylate cyclase toxins, whereas other known virulence-related factors such as the filamentous hemagglutinin, the fimbriae, and the outer membrane protein pertactin are expressed and regulated normally. Complementation and allelic exchange experiments demonstrated that the mutation is localized neither in the bvg locus involved in virulence regulation nor in the genes responsible for synthesis and transport of the toxins pertussis and adenylate cyclase. Instead, the mutation impairing transcription of at least the two toxin genes is located in a new genetic locus, which acts together with the BvgA/S two-component regulatory system on the expression of a subset of virulence genes. Further analysis suggested that most presumably the mutation affects a sequence-specific DNA-binding protein which contributes to transcriptional activation. The mutant was nonlethal in a murine respiratory model, which corresponds well with the lack of expression of the toxins. However, the clearing rate of this mutant from the lungs of mice was much lower than that of a bvg mutant, suggesting that factors other than the toxins may play a role in the persistence of the bacteria in the respiratory tract of mice.
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PMID:A phase variant of Bordetella pertussis with a mutation in a new locus involved in the regulation of pertussis toxin and adenylate cyclase toxin expression. 840 44

Two-component systems use phosphorylation reactions to regulate stimulus/response pathways. In Bordetella pertussis, a human respiratory pathogen, the infectious cycle of the organism is controlled by the BvgAS two-component system. BvgS has similarities to sensor and response regulator components and is an autophosphorylating kinase that phosphorylates BvgA. BvgA, a response regulator, is a DNA-binding protein that activates virulence gene transcription. Three phosphorylated BvgS domains, the transmitter, receiver, and C terminus, are essential for signal transduction. We now demonstrate that the BvgS transmitter is sufficient for autophosphorylation but is unable to phosphorylate the C terminus or BvgA. The BvgS receiver regulates several phenotypes: dephosphorylation of both the BvgS transmitter and C terminus as well as transfer of a phosphoryl group from the transmitter to the C terminus. Our results indicate that BvgAS signal transduction initiates with autophosphorylation of the transmitter followed by phosphotransfer to the receiver. The phosphorylated receiver can donate to the C terminus or to water. The phosphorylated C terminus is then able to transfer the phosphoryl group to BvgA.
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PMID:Central role of the BvgS receiver as a phosphorylated intermediate in a complex two-component phosphorelay. 896 72

This study describes the characterization of BpH3, a Bordetella pertussis DNA-binding protein. Sequence analysis reveals significant homology with the H-NS sequence of Escherichia coli and Haemophilus influenzae, particularly in the C-terminal part of the proteins. Our results provide evidence that H-NS and BpH3 display functional homology. First, expression of BpH3 in an hns mutant results in restoration of motility, an H-NS-dependent phenotype. This effect is dependent on the level of BpH3 expression and results from transcriptional activation of the flagellar master operon. Second, the high level of beta-glucosidase associated with hns mutations is reversed to the low wild-type level in the presence of BpH3. Third, BpH3 is able, like H-NS, to preferentially bind in vitro to curved DNA fragments, such as flhDC and bla promoter regions. Our results are the first demonstration that proteins homologous to H-NS exist in bacteria phylogenetically distant from H. influenzae and enterobacteria.
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PMID:Characterization of BpH3, an H-NS-like protein in Bordetella pertussis. 919 8

The FimZ protein, an activator of FimA production in Salmonella typhimurium, acts in conjunction with FimY to facilitate the expression of type 1 fimbriae. The predicted amino acid sequence of FimZ suggests that this protein may be a DNA-binding protein related to BvgA, a sensory regulator of virulence gene expression in Bordetella pertussis. Purification of FimZ following overexpression of the protein by a strong inducible promoter and gel mobility shift assays confirm that FimZ is a 25-kDa polypeptide that binds to the promoter region offimA. The region of DNA protected from DNase I digestion by FimZ binding is located between 47 and 98 nucleotides upstream from thefimA transcription initiation site. This region possesses a pair of 7-base pair tandem repeats, of which at least one is necessary for FimZ binding. One copy of the 7-base pair sequence is also located in thefimZ promoter region. In addition, expression from afimZ-lacZ reporter construct confirms that FimZ plays a role in its own expression. Both FimZ and FimY are required for high-level expression of FimZ, which suggests that these two fimbrial proteins are involved in regulating both FimA and FimZ.
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PMID:FimZ binds the Salmonella typhimurium fimA promoter region and may regulate its own expression with FimY. 1191 Nov 83

High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-alpha), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin.
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PMID:High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. 1696 86