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)

NF-kappa B plays a pivotal role in cells of the immune system as an inducible transcriptional activator. NF-kappa B regulates the transcription of many genes of pro-inflammatory cytokines and cell adhesion molecules, which could be involved in the pathogenesis of glomerulonephritis. Using a gel shift assay, we investigated NF-kappa B DNA-binding activity in glomeruli of WKY rats injected with nephrotoxic serum (NTS). Kinetic analysis indicated that the NF-kappa B DNA-binding activity in glomeruli, composed of p50 subunit determined by a supershift assay, increased on day 1 after NTS injection and the maximal activation was observed on day 3 to 5. NF-kappa B activation persisted at least until day 14. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappa B activation, inhibited the NTS-induced increase of glomerular NF-kappa B DNA-binding activity, followed by the inhibition of mRNA expression of IL-1 beta, MCP-1, ICAM-1 and iNOS, which are known to be regulated by NF-kappa B. PDTC also prevented urinary protein excretion which is a pathophysiological parameter for glomerulonephritis. These results suggest that NF-kappa B activation causes the induction of pro-inflammatory factors in nephritic glomeruli, which may play significant roles in the pathogenesis of glomerulonephritis.
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PMID:Activation of transcription factor NF-kappa B in experimental glomerulonephritis in rats. 867 50

RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemoattractant activity for T lymphocytes and monocytes/macrophages that are implicated in the pathogenesis of multiple sclerosis (MS) lesions. Glatiramer acetate is a drug recently approved for the treatment of MS. We therefore investigated the effect of glatiramer acetate on RANTES expression in glial cells in vitro. Treatment of human U-251 MG astroglial cells with glatiramer acetate blocks IL-1beta-induced RANTES chemokine production in a dose- and time-dependent manner. Glatiramer acetate also decreased steady-state levels of RANTES mRNA in these cells, which was attributable to reduced transcription, as assessed by nuclear run-on assays. In addition, we showed that NF-kappaB may be the transcriptional activator responsible for the IL-1beta-mediated RANTES gene expression in this system. Our data indicated that the IL-1beta-induced increase in RANTES was associated with an increase in in vitro nuclear extract binding activity specific for the NF-kappaB site in the promoter region of the RANTES gene. The increases in RANTES mRNA and protein expression were suppressed by the NF-kappaB inhibitors gliotoxin, isohelenin, and pyrrolidine dithiocarbamate (PDTC). Furthermore, we demonstrated that the increase in NF-kappaB DNA-binding activity was prevented by pretreatment with glatiramer acetate or the NF-kappaB inhibitors. Our results suggest that glatiramer acetate may inhibit IL-1beta-stimulated RANTES expression in human glial cells by blocking NF-kappaB activation, thus identifying part of the molecular basis for its anti-inflammatory and immunosuppressive effects in demyelinating diseases.
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PMID:Glatiramer acetate blocks interleukin-1-dependent nuclear factor-kappaB activation and RANTES expression in human U-251 MG astroglial cells. 1122 59

Saccharomyces cerevisiae are able to convert proline to glutamate so that it may be used as a source of nitrogen. Here, we show that the activator of the proline utilization genes, Put3p, is transcriptionally inert in the absence of proline but transcriptionally active in its presence. The activation of Put3p requires no additional yeast proteins and can occur in the presence of certain proline analogues: an unmodified pyrrolidine ring is able to activate Put3p as efficiently as proline itself. In addition, we show that a direct interaction occurs between Put3p and proline. These data, which represent direct control of transcriptional activator function by a metabolite, are discussed in terms of the regulation of proline-specific genes in yeast and as a general mechanism of the control of transcription.
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PMID:Modulation of transcription factor function by an amino acid: activation of Put3p by proline. 1451 52

Nicotine catabolism by Arthrobacter nicotinovorans is linked to the presence of the megaplasmid pAO1. Genes involved in this catabolic pathway are arranged on the plasmid into gene modules according to function. During nicotine degradation gamma-N-methylaminobutyrate is formed from the pyrrolidine ring of nicotine. Analysis of the pAO1 open reading frames (ORF) resulted in identification of the gene encoding a demethylating gamma-N-methylaminobutyrate oxidase (mabO). This gene was shown to form an operon with purU- and folD-like genes. Only in bacteria grown in the presence of nicotine could transcripts of the purU-mabO-folD operon be detected, demonstrating that this operon constitutes part of the pAO1 nicotine regulon. Its transcriptional start site was determined by primer extension analysis. Transcription of the operon was shown to be controlled by a new transcriptional regulator, PmfR, the product of a gene that is transcribed divergently from the purU, mabO, and folD genes. PmfR was purified, and electromobility shift assays and DNase I-nuclease digestion experiments were used to determine that its DNA binding site is located between -48 and -88 nucleotides upstream of the transcriptional start site of the operon. Disruption of pmfR by homologous recombination with a chloramphenicol resistance cassette demonstrated that PmfR acts in vivo as a transcriptional activator. Mutagenesis of the PmfR target DNA suggested that the sequence GTTT-14 bp-AAAC is the core binding site of the regulator upstream of the -35 promoter region of the purU-mabO-folD operon.
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PMID:Characterization of PmfR, the transcriptional activator of the pAO1-borne purU-mabO-folD operon of Arthrobacter nicotinovorans. 1583 33