Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.14.14.3 (luciferase)
38,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously identified a gene, termed Mblk-1, that encodes a putative transcription factor with two DNA-binding motifs expressed preferentially in the mushroom body of the honeybee brain, and its preferred binding sequence, termed Mblk-1-binding element (MBE) (Takeuchi, H., Kage, E., Sawata, M., Kamikouchi, A., Ohashi, K., Ohara, M., Fujiyuki, T., Kunieda, T., Sekimizu, K., Natori, S., and Kubo, T. (2001) Insect Mol Biol 10, 487-494; Park, J.-M., Kunieda. T., Takeuchi, H., and Kubo, T. (2002) Biochem. Biophys. Res. Commun. 291, 23-28). In the present study, the effect of Mblk-1 on transcription of genes containing MBE in Drosophila Schneider's Line 2 cells was examined using a luciferase assay. Mblk-1 expression transactivated promoters containing MBEs approximately 2-7-fold. Deletion experiments revealed that RHF2, the second DNA-binding domain of Mblk-1, was necessary for the transcriptional activity. Furthermore, mitogen-activated protein kinase (MAPK) phosphorylated Mblk-1 at Ser-444 in vitro, and the Mblk-1-induced transactivation was stimulated by phosphorylation of Ser-444 by the Ras/MAPK pathway in the luciferase assay. These results suggest that Mblk-1 is a transcription factor that might function in the mushroom body neuronal circuits downstream of the Ras/MAPK pathway in the honeybee brain.
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PMID:The activity of Mblk-1, a mushroom body-selective transcription factor from the honeybee, is modulated by the ras/MAPK pathway. 1263

X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). XLSA was diagnosed in a 32-year-old woman with a mild phenotype and moderately late onset. Pyridoxine therapy had no effect in the proband, but in her affected son engendered a modest increase in hemoglobin concentration and a 4-fold reduction in ferritin iron. Molecular analysis identified a C to G transversion at nucleotide -206 from the transcription start site, as defined by primer extension, in the proximal promoter region of ALAS2. No other mutations were found in the promoter region, the flanking intronic sequences, the exons, or the 3' genomic region. The same mutation was found in her affected son but not in any other of her unaffected relatives. The mutation resulted in a 94% loss of activity relative to the wild-type sequence for a luciferase reporter construct containing the proximal 293 nucleotides (nt's) of the ALAS2 promoter when transfected into human erythroid K562 cells. Confirming the mutation's deleterious effect, the ALAS2 mRNA level in the proband's erythroid precursors was reduced 87%. The mutation occurred in or near 3 different putative transcription factor binding sites of unknown erythroid importance. The dramatic decreases in reporter activity and mRNA level suggest that the region of the mutation may bind a novel and important erythroid regulatory element.
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PMID:A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. 1266 58

Cytochrome p4502C19 (CYP2C19) plays an important role in drug biotransformation and has been shown to be genetically polymorphic. While polymorphisms in the coding region that have large effects on activity are well described, until recently, a lack of knowledge of the promoter sequence has hindered efforts to study it. Genetic variants in the promoter region have not been described and factors that influence its gene expression via promotor regulation remain largely undefined. We have cloned and sequenced 1.8 kb of the human CYP2C19 promoter. This promoter contains a number of putative transcription factor sites, including HepG2-specific factor 1, glucocorticoid response element, estrogen receptor element, constitutive androstane receptor and peroxisome proliferator-activated receptor. Sequencing of DNA obtained from 67 individuals identified eight single nucleotide polymorphisms within this region. No sequence of a known human pregnane X receptor response element was found in this section of the CYP2C19 promoter, despite the known effect of rifampin on the expression of this gene. A plasmid containing the 1.8-kb CYP2C19 promoter coupled to a luciferase reporter gene has been constructed and demonstrated to be functional and sensitive to induction by omeprazole in HuH7 cells. Nested deletions of CYP2C19 promoter were generated and the ability of serial promoter deletion constructs to activate luciferase expression in the HepG2 cell line was analysed. These data make possible future studies to elucidate the molecular mechanisms by which CYP2C19 can be induced in clinical settings and the consequences of genetic variability in its promoter.
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PMID:Sequence diversity and functional characterization of the 5'-regulatory region of human CYP2C19. 1266 16

Beta-carotene 15,15'-monooxygenase (BCM) catalyzes the first step of vitamin A biosynthesis from provitamin A carotenoids. We wished to determine the factors underlying the transcriptional regulation of this gene. After cloning of the 40 kilobase pair (kbp) mouse Bcm gene and determination of its genomic organization, analysis of the 2 kb 5'-flanking region showed several putative transcription factor binding sites including TATA box, a peroxisome proliferator response element (PPRE), AP2, and bHLH. The 2 kb fragment drove specific luciferase gene expression in vitro only in cell lines that express BCM (TC7, PF11, and monkey retinal pigment epithelium). Nucleotides -41 to +163, and -60 to +163 drove basal and specific Bcm transcriptional activity, respectively. Site-directed mutagenesis and gel shift experiments demonstrate that PPRE was essential for Bcm promoter specificity and that the peroxisome proliferator activated receptor (PPAR) gamma (PPARgamma) specifically binds to this element. Furthermore, cotransfection experiments and pharmacological treatments in vitro, using the specific PPARgamma agonists LY17883 and ciglitazone, demonstrate that the PPRE element confers peroxisome proliferator responsiveness via the PPARgamma and retinoid X receptor-alpha heterodimer. Treatment of mice with the PPARalpha/gamma agonist WY14643 increases BCM protein expression in liver. Thus PPAR is a key transcription factor for the transcriptional regulation of the Bcm gene, suggesting a broader function for PPARs in the regulation of carotenoid metabolism metabolism that is consistent with their established role in neutral lipid metabolism and transport.
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PMID:Identification of beta-carotene 15, 15'-monooxygenase as a peroxisome proliferator-activated receptor target gene. 1275 35

The pathogenic processing of the amyloid precursor protein (APP) into beta-amyloid peptides, which give rise to beta-amyloid plaques in the brains of Alzheimer's disease patients, requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). We report the cloning and sequence of a 1.5-kb DNA fragment upstream of the coding sequence of the rat BACE1 gene and the construction of a BACE1 promoter/luciferase reporter construct. The basal activity of this promoter construct was highest in neuronal cell lines such as BE(2)-C and PC12 and in the pancreatic cell line AR42J, somewhat lower in rat primary neurons, and astrocytic and microglial cultures, very low in hepatocytes, and almost absent in fibroblasts and in the monocyte-macrophage cell line RAW264.7. The first 600 bp of this promoter are highly conserved among rat, mouse, and human, suggesting that this region contains regulatory elements that modulate BACE1 transcription. Indeed, this fragment contains several putative transcription factor binding sites such as MZF1, Sp1, four GATA-1 sites, and one YY1 site. Directed mutagenesis of GATA-1 elements led to altered luciferase expression, indicating that these sites are involved in the regulation of BACE1 transcription. Additionally, the analysis of promoter activities of deletion mutants suggests the presence of activators of BACE1 transcription between bases -514 to -753 and of suppressor elements between bases -754 and -1541. The BACE1 promoter sequence data and the constructs described here will be useful to identify factors that influence the expression of BACE1 in experimental paradigms in vitro.
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PMID:Cloning and expression of the rat BACE1 promoter. 1281 10

The NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is a catabolic enzyme that controls the biological activities of prostaglandins by converting them into inactive keto-metabolites. Here we report the genomic organisation of the complete human PGDH gene and characterise its transcriptional regulation. The PGDH gene spans about 31 kb on chromosome 4 and contains 7 exons. Within 2.4 kb of the 5'-flanking sequence we identified two regions with clustered putative transcription factor binding sites. The distal promoter element PGDH-DE (positions-2152/-1944 relative to the start codon) contains binding sites for Ets and activating protein-1 (AP-1) flanked by two cAMP-responsive element-binding protein binding sites (CREB1, CREB2), whereas the proximal element PGDH-PE (-235/-153) includes an Ets and an AP-1 binding sequence. By electrophoretic mobility shift assay, no high affinity binding of Ets or AP-1 factors was observed with PGDH-PE, whereas we confirmed interaction of members of the Ets, AP-1 and CREB families of transcription factors with PGDH-DE. Transcriptional control of the PGDH promoter was assessed by transiently transfecting JEG-3 choriocarcinoma cells. A luciferase reporter gene construct containing the PGDH-PE was not induced by c-jun/c-fos in the absence or presence of co-expressed Ets-1. A construct carrying the PGDH-DE in front of the minimal homologous promoter was activated by co-transfection of expression vectors for AP-1 proteins. Mutation of the AP-1 or CREB2 site reduced the response to c-jun/c-fos, whereas mutation of the Ets site of the distal element reduced basal promoter activity. CREB activated the PGDH-DE construct through the CREB1 site. These results defined the distal element as an integrator of transcriptional regulation by AP-1, Ets and CREB proteins.
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PMID:Genomic structure and transcriptional regulation of the human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase gene. 1291 29

Arabidopsis ZIM is a putative transcription factor containing an atypical GATA-type zinc-finger motif. Transcriptional activation by ZIM was tested using a transient GAL4 fusion assay and measuring the expression of a luciferase reporter in tobacco BY-2 cells. ZIM functioned as a transcriptional activator, and the transactivation domain was found to occur in its N-terminal acidic region.
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PMID:Arabidopsis ZIM, a plant-specific GATA factor, can function as a transcriptional activator. 1464 19

Walleye dermal sarcoma virus (WDSV) is a complex retrovirus found associated with tumors that appear and regress on a seasonal basis. There are quantitative and qualitative differences in the amount of virus expression between developing and regressing tumors. To understand the role of host cell factors in WDSV expression, DNase I footprint analysis, electrophoretic mobility shift assays (EMSA), and reporter gene assays were employed. DNase I footprint analysis of the U3 region of the WDSV long terminal repeat with nuclear extract prepared from a walleye cell line revealed protection of an Oct1, AP1, Whn, and two E4BP4 sites. Additionally, three regions that contained no putative transcription factor binding sites were protected. EMSA confirmed the specific binding of the protected sites and revealed three additional sites, NF1, AP3, and LVa, not protected in DNase I footprint analysis. Site-directed mutagenesis of the individual sites, in the context of a luciferase reporter plasmid, revealed that the NF1, Oct1, AP1, E4BP4#2, AP3, and LVa sites contributed to transcription activation driven by the WDSV U3 region. Mutation of Novel#2 resulted in an increase in luciferase activity, suggesting the Novel#2 site may function to bind a negative regulator of transcription. Anti-Jun and anti-Fos antiserum specifically inhibited protein-DNA complex formation, indicating the presence of c-Jun and c-Fos in the walleye cell nuclear extracts and their participation in binding to the AP1 site. Interestingly, degenerative 15-bp repeats found in the U3 region are differentially protected in DNase I footprint analysis by the walleye cell line nuclear extract and regressing-tumor nuclear extract. EMSA utilizing the 15-bp repeat probe revealed that there are similarities of binding with W12 cell and developing-tumor nuclear extracts and that the binding differs from that observed with regressing-tumor nuclear extract.
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PMID:Identification and characterization of cis-acting elements residing in the walleye dermal sarcoma virus promoter. 1522 Apr 34

Fibroblast growth factor-23 (FGF-23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site (TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and +1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin D3 in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene.
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PMID:Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells. 1567 Oct 80

In humans three isoforms of 6-phosphofructo-1-kinase (PFK) exist. Among them platelet-type PFK (PFKP) is highly abundant in the brain. With its distinct allosteric properties PFKP is regarded to be the key enzyme for the regulation of glycolysis in this organ. We cloned 1.7 kb of the 5' upstream promoter of the human PFKP gene and analyzed the promoter activity by deletion and mutation analysis using a luciferase reporter. The transcription start point was determined at 48 bp upstream of the start codon. In deletion studies the region -65 to +48 turned out to be sufficient for promoter activity while fragment -153 to +48 showed the highest promoter activity. Sequence analysis of the region from -153 to +48 revealed a stretch of eight adjacent putative transcription factor binding sites, seven of which are Sp-family specific sites. Sp1 and Sp3 were shown to bind to most if not all of them. Additionally, an NF-Y binding site was identified. Results of deletion and mutation analysis suggest that all of these transcription factors contribute positively to promoter activity. The methylation status of the promoter region was analyzed in different neural tumor cell lines and compared with that in human leukocytes and muscle.
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PMID:Characterization of the human P-type 6-phosphofructo-1-kinase gene promoter in neural cell lines. 1571 12


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