Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chemotaxis gene cluster from Treponema denticola (Td), a pathogenic spirochete associated with human periodontal diseases, was cloned, sequenced, and analyzed. The gene cluster contained three chemotaxis (che) genes (cheA, cheW, and cheY) and an open reading frame (cheX) that is homologous with Treponema pallidum (Tp) and Borrelia burgdorferi (Bb) cheX. The Td che genes have the same transcriptional orientation with a sigma 70-like promoter located upstream of cheA and a stem-loop structure characteristic of a Rho-independent transcriptional terminator downstream of cheY. Primer extension analysis identified a transcriptional start point six nucleotides (nt) downstream of the -10 (TAAAAA) promoter sequence. Reverse-transcriptase-polymerase chain reaction (RT-PCR) data indicated that cheA through cheY are co-transcribed and suggested that transcription is terminated after cheY. The gene organization of the Td che operon is identical to that of the Tp che operon. Southern blot analysis indicated the presence of one copy of each che gene on the Td genome. The cheA, cheW, cheX, and cheY genes are 2403, 1332, 462, and 438nt long, respectively, and encode proteins with predicted molecular masses of 88.2, 49.7, 16.8, and 16. 0kDa, respectively. Functional domains of the T. denticola CheA and CheY proteins are highly conserved with those of the Escherichia coli (Ec) CheA and CheY proteins. Phylogenetic analysis of Td CheY indicated that it is closely related to Tp CheY and Bb CheY3.
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PMID:Molecular characterization of a chemotaxis operon in the oral spirochete, Treponema denticola. 1033 22

Obscurin and obscurin myosin light chain kinase (MLCK) are two recently identified muscle proteins encoded by the same gene cluster. The production of obscurin, which contains a Rho-guanine exchange factor (GEF)-like sequence, and obscurin-MLCK by this cluster suggests that these novel genes may be involved in signal transduction cascades that control adaptive and compensatory responses of the heart. The goal of the present study was to investigate the transcriptional response of the obscurin gene cluster to the initiation of myocardial hypertrophy induced in mice by aortic constriction. The transcriptional activity of the obscurin genes was examined using reverse-transcriptase primed quantitative PCR. We found that the transcripts encoding the obscurin Rho-GEF and the obscurin-MLCK internal serine-threonine kinase II (SK II) domains were significantly upregulated following aortic constriction. The expression of Rho-GEF-containing transcripts at different stages of the hypertrophic growth exceeded the control levels by 2- to 6-fold. Following the induction of hypertrophy, the quantity of the SK II-encoding transcripts increased 10-fold by 24h and 16-fold by 48h, then decreased by day 7, and returned to the control level by day 56. The quantity of the carboxy terminal obscurin-MLCK transcripts encoding for SK I increased 2-fold by day 2 and returned to the control values at later stages. Immunolocalization of obscurin, which contains Rho-GEF domain, in cardiomyocytes during pharmacologically induced hypertrophic growth in vitro demonstrated that the expression was topographically associated with the growing myofibrils and with the sites of initiation and progression of myofibrillogenesis at the periphery of the sarcoplasm. This suggests that upregulation of obscurin synthesis is associated with the formation of additional amounts of contractile structures during cardiac hypertrophy. Thus, the obscurin gene cluster represents a new example of an operon that encodes differentially regulated structural and signaling proteins implicated in the control of assembly and adaptive remodeling of myofibrils during normal and hypertrophic growth.
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PMID:Rapid response of cardiac obscurin gene cluster to aortic stenosis: differential activation of Rho-GEF and MLCK and involvement in hypertrophic growth. 1455 Feb 91

We investigated the effect of fluvastatin (Flv), an HMG-CoA reductase inhibitor, on Na(+)/Ca(2+) exchanger 1 (NCX1) expression in H9c2 cardiomyoblasts. Reverse transcriptase-polymerase chain reaction analyses revealed that Flv decreased NCX1 mRNA in a concentration- and time-dependent manner and NCX1 protein. This effect of Flv was caused by the inhibition of HMG-CoA reductase, because Flv did not affect the NCX1 mRNA in the presence of mevalonate. Flv-induced down-regulation of NCX1 mRNA was also cancelled by farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), suggesting an involvement of small G-proteins. However, overexpression of neither constitutive active RhoA nor Ras affected NCX1 mRNA. In contrast, intracellular expression of C3 toxin, a specific inhibitor of Rho family proteins, decreased NCX1 mRNA, suggesting that Flv decreases NCX1 mRNA by inhibiting a signaling pathway of Rho family proteins other than RhoA. On the other hand, lysophosphatidylcholine (LPC), an activator of Rho signaling, increased both NCX1 mRNA and protein in a C3 toxin-sensitive manner. Western blot analyses revealed that membrane-associated RhoB, which is isoprenylated by either FPP or GGPP, was decreased by Flv but was increased by LPC. Selective inhibition of gene expression by short interfering RNA duplex showed that RhoB but not RhoA is involved in the regulation of NCX1 mRNA and protein. When transcription was blocked by 5,6-dichlorobenzimidazole riboside, the NCX1 mRNA stability was decreased by Flv. Long-term treatment of rat with Flv in vivo also down-regulated the cardiac NCX1 mRNA. These results suggest that a RhoB-mediated signaling pathway regulates cardiac NCX1 levels by controlling the NCX1 mRNA stability.
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PMID:Down-regulation of Na+/Ca2+ exchanger by fluvastatin in rat cardiomyoblast H9c2 cells: involvement of RhoB in Na+/Ca2+ exchanger mRNA stability. 1587 17

We have previously reported that both hypotonic stress (HTS) and lysophosphatidic acid (LPA) induce ATP release and a transient reorganization of actin through sequential activation of RhoA/Rho-kinase and focal adhesion kinase F-actin (FAK)/paxillin in human umbilical cord vein endothelial cells (HUVECs). LPA is known to induce the activation of RhoA via its specific receptors, but the mechanisms by which HTS initiates these intracellular signals are not known. The present study aimed to identify the molecule(s) that are unique to the sensing and/or transducing the mechanical stress. Reverse transcriptase-polymerase chain reaction revealed the expression of several integrin subunits in HUVECs. Anti-integrin alpha5beta1 antibody (Ab), but not anti-integrin alpha2, alpha6, alpha v, or beta4 antibodies, inhibited HTS-induced RhoA translocation, tyrosine phosphorylation of FAK and paxillin, ATP release, and actin reorganization. However, the LPA-induced ATP release and actin reorganization were not inhibited by any of these anti-integrin antibodies, indicating that integrin alpha5beta1 plays a pivotal role in the HTS-induced but not in the LPA-induced responses. It is therefore reasonable to assume that this particular subtype of integrin is involved in the initiation of the responses induced by mechanical stimuli in HUVECs.
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PMID:Pivotal role of integrin alpha5beta1 in hypotonic stress-induced responses of human endothelium. 1701 51

Neovascularization is essential for the survival and successful integration of most engineering tissues after implantation in vivo. The objective of this study was to elucidate possible mechanisms of phthalimide neovascular factor 1 (PNF1), a new synthetic small molecule proposed for therapeutic induction of angiogenesis. Complementary deoxyribonucleic acid microarray analysis was used to identify 568 transcripts in human microvascular endothelial cells (HMVECs) that were significantly regulated after 24-h stimulation with 30 muM of PNF1, previously known as SC-3-149. Network analysis tools were used to identify genetic networks of the global biological processes involved in PNF1 stimulation and to describe known molecular and cellular functions that the drug regulated most highly. Examination of the most significantly perturbed networks identified gene products associated with transforming growth factor-beta (TGF-beta), which has many known effects on angiogenesis, and related signal transduction pathways. These include molecules integral to the thrombospondin, plasminogen, fibroblast growth factor, epidermal growth factor, ephrin, Rho, and Ras signaling pathways that are essential to endothelial function. Moreover, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of select genes showed significant increases in TGF-beta-associated receptors endoglin and beta glycan. These experiments provide important insight into the pro-angiogenic mechanism of PNF1, namely, TGF-beta-associated signaling pathways, and may ultimately offer new molecular targets for directed drug discovery.
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PMID:Mechanistic exploration of phthalimide neovascular factor 1 using network analysis tools. 1772 6

To better understand the genetic control of secondary xylem formation in trees we analysed genes expressed during Eucalyptus xylem development. Using eucalyptus xylem cDNA libraries, we identified EgROP1, a member of the plant ROP family of Rho-like GTPases. These signalling proteins are central regulators of many important processes in plants, but information on their role in xylogenesis is scarce. Quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) confirmed that EgROP1 was preferentially expressed in the cambial zone and differentiating xylem in eucalyptus. Genetic mapping performed in a eucalyptus breeding population established a link between EgROP1 sequence polymorphisms and quantitative trait loci (QTLs) related to lignin profiles and fibre morphology. Overexpression of various forms of EgROP1 in Arabidopsis thaliana altered anisotropic cell growth in transgenic leaves, but most importantly affected vessel element and fibre growth in secondary xylem. Patches of fibre-like cells in the secondary xylem of transgenic plants showed changes in secondary cell wall thickness, lignin and xylan composition. These results suggest a role for EgROP1 in fibre cell morphology and secondary cell wall formation making it a good candidate gene for marker-based selection of eucalyptus trees.
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PMID:Overexpression of EgROP1, a Eucalyptus vascular-expressed Rac-like small GTPase, affects secondary xylem formation in Arabidopsis thaliana. 1954 33

Medulloblastoma is one of the common malignant brain tumors in children or young adults and its overall disease-free 5-year survival rate is approximately 50% due to tumor progression, invasion, and metastasis. This study aimed to determine whether one of Rho GTPases, Rac1 can affect the morphology, motility, and invasion of medulloblastoma cells through knockdown of Rac1 expression. Medulloblastoma Daoy cells were used to manipulate Rac1 expression using Rac1 shRNA, Rac1N17, and Rac1L61 constructs. Reverse transcriptase-PCR and western blot were used to detect expression of Rac1 mRNA and protein, respectively. Invasion and migration assays were performed to assess invasion and migration capacity of Daoy cells, respectively. The data showed that Rac1 mRNA and protein were overexpressed in Daoy cells. Deletion of Rac1 decreased the cross-linked actin network and pseudopodia and also inhibited the number of migration cells migrated or invaded to the other side of the filter compared to control cells. These data indicated that the invasion and migration in Daoy cells were inhibited by deletion of Rac1, and suggest that targeting Rac1 by Rac1 shRNA may further be evaluated and used as a potential anticancer strategy to treat medulloblastoma.
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PMID:Inhibition of tumor cell migration and invasion through knockdown of Rac1 expression in medulloblastoma cells. 2107 38