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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid hormone (PTH) regulates gene expression in skeletal osteoblasts mainly through the cAMP-protein kinase A (PKA) pathway. In neuroendocrine cells, activation of the cAMP-PKA signaling pathway leads to induction of the inducible cAMP early repressor (ICER), which is transcribed from an intronic promoter of the CREM gene and acts as a transcriptional repressor. To investigate whether PTH induces ICER expression in osteoblastic cells, RNA from MC3T3-E1 cells was subjected to reverse transcriptase-polymerase chain reaction using primers spanning the ICER sequence. Amplified products were subcloned, sequenced, and used as a probe for Northern blot analysis. In MC3T3-E1 cells, PTH induced ICER mRNA levels, which peaked at 2 h and declined to baseline by 8 h. Cycloheximide caused superinduction of ICER mRNA in response to PTH. In cultured mouse calvariae, PTH also induced ICER mRNA accumulation, which peaked at 2 h and returned almost to baseline by 10 h. Overexpression of ICER IIgamma decreased both baseline and PTH-stimulated prostaglandin G/H synthase 2 promoter activity in MC3T3-E1 cells. The induction of ICER represents a novel mechanism by which PTH regulates gene expression in osteoblastic cells.
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PMID:Parathyroid hormone induces expression of the inducible cAMP early repressor in osteoblastic MC3T3-E1 cells and mouse calvariae. 984 2

The paired-homeodomain transcription factor PAX4 is expressed in the developing pancreas and along with PAX6 is required for normal development of the endocrine cells. In the absence of PAX4, the numbers of insulin-producing beta cells and somatostatin-producing delta cells are drastically reduced, while the numbers of glucagon-producing alpha cells are increased. To gain insight into PAX4 function, we cloned a full-length Pax4 cDNA from a beta-cell cDNA library and identified a bipartite consensus DNA binding sequence consisting of a homeodomain binding site separated from a paired domain binding site by 15 nucleotides. The paired half of this consensus sequence has similarities to the PAX6 paired domain consensus binding site, and the two proteins bind to common sequences in several islet genes, although with different relative affinities. When expressed in an alpha-cell line, PAX4 represses transcription through the glucagon or insulin promoters or through an isolated PAX4 binding site. This repression is not simply due to competition with the PAX6 transcriptional activator for the same binding site, since PAX4 fused to the unrelated yeast GAL4 DNA binding domain also represses transcription through the GAL4 binding site in the alpha-cell line and to a lesser degree in beta-cell lines and NIH 3T3 cells. Repressor activity maps to more than one domain within the molecule, although the homeodomain and carboxyl terminus give the strongest repression. PAX4 transcriptional regulation apparently plays a role only early in islet development, since Pax4 mRNA as determined by reverse transcriptase PCR peaks at embryonic day 13.5 in the fetal mouse pancreas and is undetectable in adult islets. In summary, PAX4 can function as a transcriptional repressor and is expressed early in pancreatic development, which may allow it to suppress alpha-cell differentiation and permit beta-cell differentiation.
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PMID:Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. 1056 52

In this work, we characterize genes in Mycobacterium tuberculosis that are regulated by IdeR (iron-dependent regulator), an iron-responsive DNA-binding protein of the DtxR family that has been shown to regulate iron acquisition in Mycobacterium smegmatis. To identify some of the genes that constitute the IdeR regulon, we searched the M. tuberculosis genome for promoter regions containing the consensus IdeR/DxR binding sequence. Genes preceded by IdeR boxes included a set encoding proteins necessary for iron acquisition, such as the biosynthesis of siderophores (mbtA, mbtB, mbtI), aromatic amino acids (pheA, hisE, hisB-like) and others annotated to be involved in the synthesis of iron-storage proteins (bfrA, bfrB). Some putative IdeR-regulated genes identified in this search encoded proteins predicted to be engaged in the biosynthesis of lipopolysaccharide (LPS)-like molecules (rv3402c), lipids (acpP) and peptidoglycan (murB). We analysed four promoter regions containing putative IdeR boxes, mbtA-mbtB, mbI, rv3402c and bfrA-bfd, for interaction with IdeR and for iron-dependent expression. Gel retardation experiments and DNase footprinting analyses with purified IdeR showed that IdeR binds to these IdeR boxes in vitro. Analysis of the promoters by primer extension indicated that the IdeR boxes are located near the -10 position of each promoter, suggesting that IdeR acts as a transcriptional repressor by blocking RNA polymerase binding. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) coupled to molecular beacons, we showed that mRNA levels of mbtA, mbtB, mbtI, rv3402c and bfd are induced 14- to 49-fold in cultures of M. tuberculosis starved for iron, whereas mRNA levels of bfrA decreased about threefold. We present evidence that IdeR not only acts as a transcriptional repressor but also functions as an activator of bfrA. Three of the IdeR- and iron-repressed genes, mbtB, mbtI and rv3402c, were induced during M. tuberculosis infection of human THP-1 macrophages.
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PMID:The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. 1172 47

A transcriptional repressor TEL belongs to the ETS family transcription factors and acts as a tumor suppressor. We identified five alternatively spliced TEL isoforms generated possibly through exon skipping mechanisms, by using reverse transcriptase-polymerase chain reaction analysis. Among them, we examined molecular and biological functions of a DeltaETS-TEL isoform (TEL-f). This isoform abrogated specific DNA-binding capacity to and trans-repressional ability through the ETS-binding site. Regardless, it showed dominant-negative effects over wild-type-TEL (TEL-a)-mediated transcriptional repression partly through sequestration of TEL-a from nucleus to cytoplasm. Moreover, TEL-f dominantly interfered with TEL-a-mediated erythroid differentiation in MEL cells and growth suppression in NIH3T3 cells. Interestingly, TEL isoforms without the entire (Delta exons 6+7-TEL) or a part (Delta exon 7-TEL) of ETS domain were expressed more frequently in myelodysplastic syndrome-derived leukemia than in myelodysplastic syndrome before transformation. This observation suggests that accumulation of the dominant-negative DeltaETS-TEL molecules could be a related phenomenon to leukemic progression of myelodysplastic syndrome.
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PMID:Functional analysis of a dominant-negative DeltaETS TEL/ETV6 isoform. 1509 86

The expression of iron regulated genes in bacteria is typically controlled by the ferric uptake regulator (Fur) protein, a global transcriptional repressor that regulates functions as diverse as iron acquisition, oxidative stress, and virulence. We have identified a fur homologue in Dichelobacter nodosus, the causative agent of ovine footrot, and shown that it complements an Escherichia coli fur mutant. Homology modeling of the D. nodosus Fur protein with the recently solved crystal structure of Fur from Pseudomonas aeruginosa indicated extensive structural conservation. As Southern hybridization analysis of different clinical isolates of D. nodosus indicated that the fur gene was present in all of these strains, the fur gene was insertionally inactivated to determine its functional role. Analysis of these mutants by various techniques did not indicate any significant differences in the expression of known virulence genes or in iron-dependent growth. However, we determined several Fur regulatory targets by two-dimensional gel electrophoresis coupled with mass spectrometry. Analysis of proteins from cytoplasmic, membrane, and extracellular fractions revealed numerous differentially expressed proteins. The transcriptional basis of these differences was analyzed by using quantitative reverse transcriptase PCR. Proteins with increased expression in the fur mutant were homologues of the periplasmic iron binding protein YfeA and a cobalt chelatase, CbiK. Down-regulated proteins included a putative manganese superoxide dismutase and ornithine decarboxylase. Based on these data, it is suggested that in D. nodosus the Fur protein functions as a regulator of iron and oxidative metabolism.
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PMID:Identification of a Dichelobacter nodosus ferric uptake regulator and determination of its regulatory targets. 1560 21

Abortive infection mechanisms of Lactococcus lactis form a heterogeneous group of phage resistance systems that act after early phage gene expression. One of these systems, AbiK, aborts infection of the three most prevalent lactococcal phage groups of the dairy industry. In this study, it is demonstrated that the antiphage activity depends on the level of expression of the abiK gene and on the presence of a reverse transcriptase (RT) motif in AbiK. The abiK gene was shown to be part of an operon that includes two additional open reading frames, with one of these encoding a phage-related transcriptional repressor named Orf4. Expression of AbiK is driven by two promoters, PabiK and Porf3, the latter being repressed by Orf4 in vivo. Binding of the purified Orf4 to the Porf3 promoter was demonstrated in vitro by gel retardation assays. The N-terminal half of the deduced AbiK protein possesses an RT motif that was modified by site-directed mutagenesis. Conservative mutations in key positions resulted in the complete loss of the resistance phenotype. These data suggest that an RT activity might be involved in the phage resistance activity of AbiK. A model for the mode of action of AbiK is proposed.
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PMID:Expression and site-directed mutagenesis of the lactococcal abortive phage infection protein AbiK. 1590 96

Telomerase activity is suppressed in normal human somatic tissues but is activated in cancer cells and immortal cell lines. The reverse transcriptase (RT) subunit human telomerase reverse transcriptase (hTERT) is the key regulator of telomerase activity. The hTERT promoter contains E-box elements and may allow upstream stimulatory factor (USF), a basic helix-loop-helix (bHLH) leucine zipper family proteins, to bind and regulate the expression. In this study, we investigated whether and how USF effect on hTERT. Through luciferase reporter assays, we found that both USF1 and USF2 possess a comparable effect on the inhibition of hTERT expression. Immunoprecipitation (IP) and immunoblotting (IB) analysis reveal that the suppression of hTERT by USF was not through the interaction of USF with c-myc or mad, nor disturbed the cellular protein levels of those. In gel mobility shift and chromatin immunoprecipitation (CHIP) assays, we found that the USF suppression is through direct binding at the E-box site of hTERT promoter and rendering the effect actively. Analysis on clinical normal and tumor tissues reveal that the expression of USF1 and USF2 was lower in the tumor tissues, correlated with hTERT expression and telomerase activity. Taking together, our results demonstrate that USF is a negative transcriptional repressor for hTERT in oral cancer cells. It is possible that USF lose the inhibitory effect on hTERT expression leading to telomerase reactivation and oral carcinogenesis.
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PMID:Upstream stimulatory factor (USF) as a transcriptional suppressor of human telomerase reverse transcriptase (hTERT) in oral cancer cells. 1601 Jun 90

Bartonella quintana is a gram-negative agent of trench fever, chronic bacteremia, endocarditis, and bacillary angiomatosis in humans. B. quintana has the highest known hemin requirement among bacteria, but the mechanisms of hemin acquisition are poorly defined. Genomic analyses revealed a potential locus dedicated to hemin utilization (hut) encoding a putative hemin receptor, HutA; a TonB-like energy transducer; an ABC transport system comprised of three proteins, HutB, HutC, and HmuV; and a hemin degradation/storage enzyme, HemS. Complementation analyses with Escherichia coli hemA show that HutA functions as a hemin receptor, and complementation analyses with E. coli hemA tonB indicate that HutA is TonB dependent. Quantitative reverse transcriptase PCR analyses show that hut locus transcription is subject to hemin-responsive regulation, which is mediated primarily by the iron response regulator (Irr). Irr functions as a transcriptional repressor of the hut locus at all hemin concentrations tested. Overexpression of the ferric uptake regulator (fur) represses transcription of tonB in the presence of excess hemin, whereas overexpression of the rhizobial iron regulator (rirA) has no effect on hut locus transcription. Reverse transcriptase PCR analyses show that hutA and tonB are divergently transcribed and that the remaining hut genes are expressed as a polycistronic mRNA. Examination of the promoter regions of hutA, tonB, and hemS reveals consensus sequence promoters that encompass an H-box element previously shown to interact with B. quintana Irr.
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PMID:Function, regulation, and transcriptional organization of the hemin utilization locus of Bartonella quintana. 1898 Dec 45

Three genes, nadA, nadB, and nadC, involved in NAD de novo biosynthesis are broadly conserved in the genomes of numerous bacterial species. In the genome of Corynebacterium glutamicum, nadA and nadC but not nadB are annotated. The nadA and nadC genes are located in a gene cluster containing two other genes, designated ndnR and nadS herein. ndnR encodes a member of the Nudix-related transcriptional regulator (NrtR) family. nadS encodes a homologue of cysteine desulfurase involved in Fe-S cluster assembly. The gene cluster ndnR-nadA-nadC-nadS is genetically characterized herein. Mutant strains deficient in nadA, nadC, or nadS required exogenous nicotinate for growth, and the nicotinate auxotrophy was complemented by introduction of the corresponding gene in trans, indicating that each of these genes is essential for growth in the absence of an exogenous source of NAD biosynthesis. The results of reverse transcriptase PCR analyses and ndnR promoter-lacZ expression analyses revealed that the expression of ndnR, nadA, nadC, and nadS genes was markedly and coordinately repressed by nicotinate. The expression of these genes was enhanced by the disruption of ndnR, resulting in the loss of the nicotinate-responsive regulation of gene expression. These results suggest that NdnR acts as a transcriptional repressor of NAD de novo biosynthesis genes and plays an essential role in the regulation of the response to nicotinate.
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PMID:Regulation of the expression of genes involved in NAD de novo biosynthesis in Corynebacterium glutamicum. 2060 9

The bed nucleus of the stria terminalis (BNST) plays a critical role in regulating the behavioral response to stress. Stressors that activate the BNST also activate serotonergic (5-HT) systems. Hence, maladaptive changes of 5-HT receptor expression may contribute to stress-induced anxiety disorders. The BNST contains three neuronal types, Type I-III neurons. However, little is known about 5-HT receptor subtypes mRNA expression in these neurons, or whether it can be modulated by stress. Whole-cell patch clamp recording from Type I-III neurons was used in conjunction with single cell reverse transcriptase polymerase chain reaction (RT-PCR) to characterize 5-HT receptor mRNA expression, and examine the effects of stress on this expression. We report that Type I neurons expressed mRNA transcripts predominantly for 5-HT(1A) and 5-HT(7) receptors. Type II neurons expressed transcripts for every 5-HT receptor except the 5-HT(2C) receptor. Type II neurons were divided into three sub-populations: Type IIA in which transcripts for 5-HT(3) and 5-HT(7) receptors predominate, Type IIB that mainly express 5-HT(1B) and 5-HT(4) receptor transcripts, and Type IIC in which transcripts for 5-HT(1A) and 5-HT(2A) receptors predominate. Type III neurons were also subdivided into two sub-populations; one that predominantly expressed transcripts for 5-HT(1A), 5-HT(1B) and 5-HT(2A) receptors, and another that mainly expressed transcripts for 5-HT(2C) receptor. Unpredictable shock stress (USS) caused a long-lasting increase in anxiety-like behavior, and a concomitant decrease in 5-HT(1A) transcript expression in Type I-III neurons, as well as an up-regulation of a transcriptional repressor of 5-HT(1A) gene expression, deformed epidermal autoregulatory factor 1 (Deaf-1). Significantly USS decreased 5-HT(1A) protein level, and increased the level of Deaf-1. USS also increased 5-HT(1B) transcript expression in Type III neurons, as well as 5-HT(7) expression in Type I and II neurons. These data suggest that cell type-specific disruption of 5-HT receptor expression in BNST(ALG) neurons may contribute to stress-induced anxiety disorders.
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PMID:Differential distribution of serotonin receptor subtypes in BNST(ALG) neurons: modulation by unpredictable shock stress. 2292 22


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