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)

Sequences which control basal human T-cell lymphotropic virus type I (HTLV-I) transcription probably play an important role in initiation and maintenance of virus replication. We have identified and analyzed a 45-nucleotide sequence (downstream regulatory element 1 [DRE 1]) at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription. The basal promoter strength of constructs that contained deletions in the R/U5 region of the HTLV-I long terminal repeat were analyzed by chloramphenicol acetyltransferase assays following transfection of Jurkat T cells. We consistently observed a 10-fold decrease in basal promoter activity when sequences between +202 to +246 were deleted. By reverse transcriptase polymerase chain reaction RNA analysis, we confirmed that the drop in chloramphenicol acetyltransferase activity was paralleled by a decrease in the level of steady-state RNA. DRE 1 did not affect the level of Tax1 transactivation. Using a gel shift assay, we have purified a highly enriched fraction that could specifically bind DRE 1. This DNA affinity column fraction contained four detectable proteins on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis: p37, p50, p60, and p100. The affinity column fraction stimulated HTLV-I transcription approximately 12-fold in vitro. No effect was observed with the human immunodeficiency virus or adenovirus major late promoters. Following renaturation of the proteins isolated from an SDS-containing gel, p37, but not the other protein fractions, was able to specifically bind to DRE 1.
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PMID:Sequences downstream of the RNA initiation site regulate human T-cell lymphotropic virus type I basal gene expression. 847 78

In this study we have found that endothelial cells from different origins all contain a CD44-related transmembrane glycoprotein, named GP116. Using a bovine aortic endothelial cell line and a standard pulse-chase protocol, we show that GP116 is synthesized as a 52-kDa nascent polypeptide precursor (p52) which is processed to GP116 as follows, p52 --> p63/65 --> p82 --> p100 --> GP116. GP116 contains approximately 8 N- and approximately 11 O-linked oligosaccharide chains (but lacks glycosaminoglycans) and interacts directly with the cytoskeletal protein, ankyrin, both in vitro (Kd approximately 1.2 nM) and in vivo. The results of GP116 amino acid composition, reverse transcriptase-polymerase chain reaction, Southern blot, Northern blot, cloning, and sequence analyses indicate that endothelial cells express this new CD44 variant that contains an exon having significant homology with human CD44 exon 14 (ex14/v10). GP116, designated as CD44 (ex14/v10), has been shown to be a major hyaluronic acid (HA) receptor (Kd approximately 0.5-0.8 nM) responsible for cell adhesion. Most importantly, we have found that the interaction between CD44(ex14/v10) and HA or a small fragment of HA (10-15 disaccharide units) induces a mitogenic response in endothelial cells. These findings suggest that this CD44 variant plays an important role in regulating endothelial cell proliferation.
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PMID:The cell adhesion molecule, GP116, is a new CD44 variant (ex14/v10) involved in hyaluronic acid binding and endothelial cell proliferation. 879 16

Establishment of infection and disease implies modifications in the genetic programmes of the cell systems that are involved and the differential expression of genes in both parasite and host. In order to identify and isolate relevant genes of the fungus, Histoplasma capsulatum, in which expression is specifically induced during its interaction with murine macrophages (Mphi), we performed a comparative analysis of the pattern of gene expression of the fungus before and after exposure to, and internalization into Mphi by using differential display reverse transcriptase-PCR (DDRT-PCR). Using a limited set of primer combinations, six cDNA fragments of H. capsulatum were identified and isolated; five representing fungal genes in which expressions were enhanced during Mphi infection, whereas one mRNA fragment was down-regulated. Slot blots followed by Northern blot analyses confirmed that the transcripts detected with cDNA clones were over expressed after 1 h of Mphi infection, whereas no transcripts were detected with mRNA purified from H. capsulatum before infection. Sequence analyses and database searches revealed no significant homology to any known sequence for five of these clones. One of the clones showed homology to the rat p105 kD protein, and to the p100 kD co-activator proteins of human and Caenorhabditis elegans. To our knowledge, this is the first experimental evidence that specific genes are differentially expressed by a fungal pathogen when it is exposed to, and phagocytosed by Mphi. Furthermore, these results show that the DDRT-PCR procedure has adequate sensitivity to detect fungal genes induced during parasite-host interaction to identify potential new targets that can be used to develop new antifungal drugs.
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PMID:Identification and isolation by DDRT-PCR of genes differentially expressed by Histoplasma capsulatum during macrophages infection. 971 85

Cyclooxygenase-2 expression by malignant tumors, including colonic adenocarcinoma, is associated with increased tumor aggression and poor prognosis. Nuclear factor kappa B is a key regulator of cyclooxygenase-2 and is regulated by two pathways, the 'canonical' and the 'alternative' pathway. The alternative pathway is triggered by members of the tumor necrosis factor cytokine family, including RelB and p52. This present study was undertaken to evaluate cyclooxygenase-2 and the alternative nuclear factor-kappa B signaling pathway in colonic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue samples diagnosed with colonic adenocarcinoma and a human colonic adenocarcinoma cell line, LS174, were studied. The expression of cyclooxygenase-2, RelB and p52 were determined using immunohistochemistry, immunofluorescence, and Western blots. Quantitative analysis of mRNA by real-time reverse transcriptase polymerase chain reaction and chromatin immunoprecipitation were performed on the tissue and cell samples. To investigate nuclear factor kappa B gene regulation of the cyclooxygenase-2 gene, dual luciferase assays were performed, and LS174 cells were transfected with RelB or p100/p52 short interfering RNA. Upregulation of cyclooxygenase-2 was associated with activation of the alternative nuclear factor kappa B signaling pathway components RelB, and p52, in colonic adenocarcinoma cells in tissues and the cell line, LS174. Chromatin immunoprecipitation assay determined that cyclooxygenase-2 gene was associated with both RelB and p52. A luciferase reporter assay showed that the nuclear factor kappa B enhancer of cyclooxygenase-2 was sufficient to regulate the transcriptional activity of a heterologous promoter in LS174 cells. RNA interference-mediated knockdown of RelB or p52 resulted in significant inhibition of cyclooxygenase-2 at both mRNA and protein levels in LS174 cells. These findings support a potential role for inhibition of components of the alternative nuclear factor kappa B signaling pathway, RelB-p52-cyclooxygenase-2, as a possible therapeutic target in the treatment of adenocarcinoma of the colon. Further studies on the role of this pathway in this and other malignancies are recommended.
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PMID:Upregulation of cyclooxygenase-2 is associated with activation of the alternative nuclear factor kappa B signaling pathway in colonic adenocarcinoma. 2655 Apr 60