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)

HIV-1 reverse transcriptase (RT) is multifunctional, with RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) activities. N-(4-tert-Butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone (BBNH) inhibited both the polymerase and the RNase H activities of HIV-1 RT in vitro. IC50 values for inhibition of RDDP were 0.8-3.4 microM, depending on the template/primer (T/P) used in the assay. The IC50 for DDDP inhibition was about 12 microM, while that for inhibition of RNase H was 3.5 microM. EC50 for inhibition of HIV-1 replication in cord blood mononuclear cells was 1.5 microM. BBNH inhibition of RNase H in vitro was time-dependent, whereas inhibition of RT polymerase activities was immediate. BBNH was a linear mixed-type inhibitor of RT RDDP activity with respect to both T/P and to dNTP, whereas BBNH inhibition of RT RNase H activity was linear competitive. Protection experiments using an azidonevirapine photolabel showed that BBNH binds to the non-nucleoside RT inhibitor (NNRTI) binding pocket. Importantly, the compound inhibited recombinant RT containing mutations associated with high-level resistance to other NNRTI. While BBNH did not inhibit the DNA polymerase activities of other retroviral reverse transcriptases and DNA polymerases, the compound inhibited Escherichia coli RNase HI and the RNase H activity of murine leukemia virus RT. BBNH also inhibited HIV-1 RT RNase H in the presence of high concentrations of other non-nucleoside inhibitors with higher affinities for the NNRTI binding pocket, and of RT in which the NNRTI binding pocket had been irreversibly blocked by the azidonevirapine photolabel. We conclude that BBNH may therefore bind to two sites on HIV-1 RT. One site is the polymerase non-nucleoside inhibitor binding site and the second may be located in the RNase H domain. BBNH is therefore a promising lead compound for the development of multisite inhibitors of HIV-1 RT.
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PMID:Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone. 911 94

Gonadotropin-releasing hormone (GnRH) is encoded by the proGnRH gene which contains four exons and three introns. In this study, two immortalized GnRH-expressing cell lines (Gn11 and NLT) were characterized. The NLT and Gn11 cells, derived from a same brain tumor in a transgenic mouse, display neuronal morphology and neuron-specific markers. However, NLT cells secrete much higher levels of GnRH than Gn11 cells. To delineate the mechanism underlying this difference, reverse transcriptase-polymerase chain reaction and RNase protection assays were performed to examine proGnRH gene expression. While the mature proGnRH mRNA was predominately expressed in NLT cells, Gn11 cells express an abundant short transcript. Sequence analysis revealed that this short transcript contains exons 1, 3, and 4, but not exon 2, which encodes the GnRH decapeptide. RNase protection assays demonstrated that NLT cells express much higher levels of mature proGnRH mRNA than Gn11 cells. The lower level of GnRH secreting capacity in Gn11 cells is due, in part, to decreased expression of mature proGnRH mRNA. When proGnRH gene expression in the mouse brain was examined, the same short splicing variant was observed in the olfactory area and preoptic area-anterior hypothalamus. But the prevalent transcript in these regions was the mature proGnRH mRNA. In contrast, only the mature proGnRH mRNA was found in the caudal hypothalamus. These results suggest that alternative splicing may be one of the mechanisms regulating proGnRH gene expression in the animal brain.
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PMID:An alternative gonadotropin-releasing hormone (GnRH) RNA splicing product found in cultured GnRH neurons and mouse hypothalamus. 913 17

Several techniques were used to study the co-ordination of mRNA levels for five constituent chains of cartilage collagen fibrils during mouse development. Short cDNA clones were first constructed for mouse and human alpha3(IX) and for mouse proalpha1(XI) collagen mRNA species. Northern analysis of developing mouse embryos revealed that the mRNA species for alpha1, alpha2 and alpha3 chains of type IX collagen peaked earlier than those for proalpha1(II) and proalpha1(XI) collagen chains. Quantification of these mRNA species by slot-blot hybridization confirmed this developmental regulation: the mRNA ratios for type II/type IX/type XI collagens changed from 5.7:1:0.6 (at embryonic day 12.5) to 10.6:1:0.9 (in newborn mice). However, the genes coding for the three chains of type IX collagen seemed to be under more co-ordinated regulation during mouse development. In addition to high mRNA levels in cartilages and the eye, low levels of type IX collagen transcripts were identified in brain and skin of newborn mouse using RNase protection and reverse transcriptase-PCR assays. Finally, hybridization in situ revealed identical tissue distributions of the three type IX collagen mRNA species during early chondrogenesis but somewhat more widespread expression of the alpha1(IX) and alpha3(IX) mRNA species during endochondral ossification at day 16.5 of embryonic development. These results suggest a relatively tight co-ordination of the alpha1(IX), alpha2(IX), and alpha3(IX) collagen mRNA species in chondrocytes, but a lack of co-ordination in several non-cartilaginous tissues.
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PMID:Developmental regulation of mRNA species for types II, IX and XI collagens during mouse embryogenesis. 916 58

The gene AML1/PEBP2 alphaB encodes the alpha subunit of transcription factor PEBP2/CBF and is essential for the establishment of fetal liver hematopoiesis. Rearrangements of AML1 are frequently associated with several types of human leukemia. Three types of AML1 cDNA isoforms have been described to date; they have been designated AML1a, AML1b, and AML1c. All of these isoforms encode the conserved-Runt domain, which harbors the DNA binding and heterodimerization activities. We have identified a new isoform of the AML1 transcript, termed AML1 deltaN, in which exon 1 is directly connected to exon 4 by alternative splicing. The AML1 deltaN transcript was detected in various hematopoietic cell lines of lymphoid to myeloid cell origin, as revealed by RNase protection and reverse transcriptase PCR analyses. The protein product of AML1 deltaN lacks the N-terminal region of AML1, including half of the Runt domain, and neither binds to DNA nor heterodimerizes with the beta subunit. However, AML1 deltaN was found to interfere with the transactivation activity of PEBP2, and the molecular region responsible for this activity was identified. Stable expression of AML1 deltaN in 32Dcl3 myeloid cells blocked granulocytic differentiation in response to granulocyte colony-stimulating factor. These results suggest that AML1 deltaN acts as a modulator of AML1 function and serves as a useful tool to dissect the functional domains in the C-terminal region of AML1.
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PMID:A novel transcript encoding an N-terminally truncated AML1/PEBP2 alphaB protein interferes with transactivation and blocks granulocytic differentiation of 32Dcl3 myeloid cells. 919 49

The channel properties of the multimeric ionotropic glutamate receptors can be regulated by their subunit composition. The relationship between the structure and physiological functions of glutamate receptors, however, is difficult to study in the CNS because of the large number of these subunits, their widespread distribution, and neuronal heterogeneity. To avoid these difficulties, and to uncover possible novel functions of ionotropic glutamate receptors in sensory neurons, we examined the expression of non-N-methyl-D-aspartate glutamate receptor subunits in a simple neuronal system: the olfactory epithelium. It contains only one neuronal type, the olfactory receptor neuron, that receives no synaptic innervation within the epithelium and therefore should not require conventional postsynaptic glutamate receptors. The axons of these neurons, however, terminate and release glutamate in the glomerular region of the olfactory bulb, and may contain presynaptic glutamate receptors. By reverse transcriptase-polymerase chain reaction amplification and RNase protection assays, we showed that a subset of non-N-methyl-D-aspartate receptor subunits is expressed in the olfactory epithelium. The most abundant is KA2, which can form kainate-selective ion channels with GluR5 or GluR6. Messenger RNAs for GluR6, and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate-type (AMPA/KA) GluR2 and GluR3 subunits, are also present, but at levels lower than that of KA2 by an order of magnitude. In situ hybridization and immunocytochemistry localized KA2 to only the olfactory receptor neurons, and not to any other cell type in the olfactory epithelium. Surprisingly, antibodies against KA2 or GluR5/6/7 primarily stained the olfactory neuron dendritic knobs that are specialized for odorant signalling at the sensory epithelial lumenal surface, and the olfactory neuron axon bundles that project to the olfactory bulb. The presence of a limited subset of non-N-methyl-D-aspartate receptor subunits in the olfactory epithelium, and the localization of a kainate-selective receptor to both the axons and specialized dendritic knobs of olfactory receptor neurons, which receive no known synaptic input, suggest that these non-N-methyl-D-aspartate receptor subtypes may mediate either novel non-synaptic functions in the olfactory neuron dendrites or presynaptic functions in the olfactory nerve terminals or axons. These data also suggest that the olfactory sensory system, possessing a relatively simple anatomical organization and a limited number of glutamate receptor subunits, may be useful for elucidating facets of the complex relationships between subunit composition and physiological function of ionotropic glutamate receptors.
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PMID:Expression of non-N-methyl-D-aspartate glutamate receptor subunits in the olfactory epithelium. 920 Jul 25

Expression of the follistatin (FS) and inhibin/activin (I/A) alpha, beta(A), and beta(B) subunit genes in porcine ovarian follicles was evaluated by reverse transcriptase polymerase chain reaction and/or RNase protection procedures to establish changes during the final stages of follicular development. For the I/A alpha and beta(A) subunits, expression increased (p < 0.05) as follicles progressed to the mid-stage of the follicular phase. The beta(B) subunit was expressed in lower concentrations, and all three I/A subunits showed a marked reduction (p < 0.01) in expression by the late stage of follicular development. In contrast to this pattern, FS gene expression decreased (p < 0.05) as follicles developed from the early (low estradiol) to the mid stage (high estradiol) and continued to decline in advanced follicles (after estrus). The predominant mRNA encoded for FS-315, and the ratio of mRNA for FS-315 to mRNA for FS-288 did not differ significantly during the three stages. Within an animal, concentration of FS mRNAs was related more to stage of the follicular phase than to follicular size. Follicular fluid concentration of FS changed in a manner similar to that observed for expression of its gene. We conclude that expression of the FS gene and translation of its mRNA decrease as follicles approach ovulatory status.
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PMID:Expression of follistatin and inhibin/activin subunit genes in porcine follicles. 920 88

The nucleotide and derived amino acid sequences of tammar preprorelaxin were established by combined reverse transcriptase polymerase chain reaction and 3'- and 5'-rapid amplification of cDNA ends methods, using RNA from the corpus luteum of late pregnancy as template. Relaxin gene expression was then investigated in tissues at various stages of the 26-day pregnancy and in adult males. The full-length tammar relaxin preprohormone is 579 base pairs. The derived amino acid sequence contains a probable signal peptide of 26 amino acids, a B-domain of 31 amino acids, a C-domain of 111 amino acids, and an A-domain of 24 amino acids, with sequence homologies of 49%, 38%, 47%, and 47%, respectively, to dogfish, pig, and both human relaxins, for the combined A- and B-domains of the functional peptides. The conserved amino acid residues in the B-domain confirm a region shown to be essential for binding of the peptide to its receptor. A relaxin gene is expressed in several other tissues of pregnant tammars including the placenta, follicle, and hypothalamus. Northern analysis showed a 1-kilobase relaxin transcript in the corpus luteum and placenta. Using RNase protection assays, relaxin gene expression in the corpus luteum was greater in early and mid pregnancy, reduced at term, and absent postpartum. These data demonstrate relaxin biosynthesis in both the corpus luteum and placenta in this marsupial and suggest that a relaxin physiology has been conserved during mammalian evolution.
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PMID:Marsupial relaxin: complementary deoxyribonucleic acid sequence and gene expression in the female and male tammar wallaby, Macropus eugenii. 920 89

Glucocorticoids (GCH) are highly effective agents in controlling inflammation and immune response. We studied the effect of the synthetic GCH dexamethasone (DEX) on the expression of TCR zeta gene splicings that code for some chains belonging to the T-cell receptor (TCR)/CD3 complex. In the DEX-treated hybridoma T-cell line 3DO, TCR zeta gene splicings increase within the first 24 hr (about fourfold increase), as demonstrated by reverse transcriptase-polymerase chain reaction and RNase protection assay. This increase is due to the stimulation of TCR zeta gene locus transcription, as demonstrated by the "run-on" assay. A similar upregulation was observed in murine thymocytes following in vivo DEX treatment. As a consequence of TCR zeta gene locus modulation, the expression of the spliced mRNAs coding for TCR zeta and TCR eta subunits is increased, whereas their relative ratio is only slightly changed. Indeed, the amount of TCR zeta protein in 24-hr DEX-treated cells is fivefold more than that in the untreated cells. A similar effect was seen in 3DO cells treated with hydrocortisone but not in those treated with testosterone. TCR zeta protein increase was confined to the cytoplasm and therefore TCR/CD3 complex expression did not increase. This newly described effect of DEX may constitute an additional molecular mechanism that contributes to its immunomodulating activity.
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PMID:Short-term dexamethasone treatment modulates the expression of the murine TCR zeta gene locus. 922 3

The expression of the ob gene product leptin in adipose tissues has been previously described to be regulated by insulin in vivo and vitro. Akt, a ser/thr kinase with a pleckstrin homology domain, has recently been identified to function in the insulin receptor signaling cascade. The aim of this study was to investigate the role of Akt in the production of leptin by adipocytes. Therefore, we examined leptin production by 3T3-L1 adipocytes stably expressing a myristoylated version of Akt which is constitutively active. Leptin levels in the supernatants of serum starved, nonstimulated 3T3-L1 adipocytes were determined by radioimmunoassay (RIA). Expression of the constitutively active Akt was found to induce a more than 20-fold increase in leptin levels whereas a control non-myristoylated Akt had no effect. Leptin mRNA levels as determined by either RNase protection assay or reverse transcriptase (RT)-polymerase chain reaction (PCR) were not elevated by the constitutively active Akt. These results indicate that Akt can induce leptin production in 3T3-L1 adipocytes via a non-transcriptional mechanism.
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PMID:A constitutively active version of the Ser/Thr kinase Akt induces production of the ob gene product, leptin, in 3T3-L1 adipocytes. 923 12

We have cloned the mouse CCK-A receptor gene (Cckar), determined its nucleotide sequence, and analyzed its expression. The receptor protein is encoded in five exons distributed over 9 kb of genomic DNA. Intron/exon borders were determined by comparing the genomic nucleotide sequence with the mouse cDNA sequence obtained by reverse transcriptase polymerase chain reaction. RNase protection analysis of Cckar transcripts revealed the presence of a splice acceptor site 200 bp upstream of the translational start codon, indicating that the promoter is associated with a non-translated exon at an upstream site. The second coding exon contains a rarely used alternative splice site that would result in the production of a truncated, 48 amino acid protein. Cckar is widely expressed in the gastrointestinal system (pancreas, gallbladder, intestine, colon and stomach), as well as in brain and kidney.
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PMID:Molecular structure of the mouse CCK-A receptor gene. 924 2


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