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)

A Trypanosoma brucei repeated DNA element (TRS-1, for trypanosome repeated sequence), which seems transposable, may encode a 1651 amino acid polypeptide showing homology with reverse transcriptase. This polypeptide would also carry a DNA-binding domain, as suggested by the presence of five DNA-binding "fingers" homologous to those of the transcription factor TFIIIA of Xenopus laevis and retroviral DNA-binding proteins.
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PMID:DNA-binding fingers encoded by a trypanosome retroposon. 244 94

hLH-2, a transcription factor that contains double cysteine rich regions (LIM motifs) and a homeobox (Hox) DNA-binding domain shows aberrant high expression in all cases of chronic myelogenous leukemia (CML). This gene has been mapped to the chromosome 9q33-34.1, the same region as the reciprocal translocation that creates the breakpoint cluster region (BCR)-ABL chimera of the Philadelphia chromosome (Ph'). To investigate the possible involvement between the BCR-ABL fusion gene and hLH-2 in the pathogenesis of CML, an hLH-2-negative CML cell line, JK-1 that carries double Ph' chromosomes, was examined. Like other CML cells, high BCR-ABL fusion mRNA levels are expressed, but no transcript of hLH-2 was detected in JK-1 cells as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the CML cell line, K-562, an additional rearrangement of the BCR gene was observed in JK-1 as determined by Southern blot hybridization; however, the hLH-2 gene was normal. These findings raise interesting questions about the possible roles of either the abnormal BCR gene or other genetic events such as the complex chromosomal abnormalities that result in hLH-2 being turned off in JK-1 cells.
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PMID:A structurally abnormal breakpoint cluster region gene in a transcription factor, hLH-2-negative human leukemia cell line. 760 May 33

ER mRNA was detected as 6.0 kb band by Northern blot analysis in vascular smooth muscle cells (VSMC) derived from rat aorta. The presence of ER mRNA in VSMC was confirmed by reverse transcriptase-polymerase chain reaction using specific primers for rat ER cDNA. In addition, the immunocytochemistry of ER was performed in VSMC using a monoclonal anti-ER antibody which recognizes DNA-binding domain of ER. The immunoreactivity was distributed in the cytoplasm as well as in the nuclei. Thus, the expression of ER in VSMC was demonstrated at both the protein and the mRNA level. Furthermore, the expression of c-fos mRNA in VSMC was found up-regulated by 17 beta-estradiol treatment within 30 min. The observation that VSMC possess ER and respond to estrogen supports the idea that estrogen may directly influence vascular cell system through the ER.
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PMID:Vascular smooth muscle cells as target for estrogen. 769 May 60

Several previously unnoticed genes in the human immunodeficiency virus type 1 (HIV-1), potentially encoding selenoproteins, have been discovered by analyzing the genomic RNA structure and its relation to novel open reading frames. We have found a number of new potential RNA pseudoknots, including one in the long terminal repeat, several that coincide with highly conserved enzyme active site sequences in the pol coding region, and one in the env coding region. These pseudoknots can potentially direct the synthesis of selenocysteine (SeC) containing--1 frameshift fusion proteins. This is possible because we have found potential SeC insertion sequences (SECIS) in the RNA of HIV and other retroviruses; such structures are known to be necessary and sufficient for the incorporation of SeC at UGA "stop" codons anywhere in a eukaryotic mRNA. In several locations, UGA codons in the -1 reading frame are highly conserved across a broad spectrum of primate immunodeficiency viruses. Due to the degeneracy of the genetic code, this conservation cannot be explained by evolutionary selection of the pol gene protein sequence alone. Such observations, combined with the conservation of the associated reading frames, strongly suggest that these are real genes, and thus that the pseudoknots are also real. A protease pseudoknot-directed -1 frameshift fusion protein contains a highly conserved SeC codon and has significant similarities to a number of DNA binding proteins, including papillomavirus E2 proteins, suggesting it may be a virally encoded repressor of HIV transcription when cleaved by protease from the rest of the gag-pol gene product. A reverse transcriptase (RT) frameshift fusion protein replaces the RT active site with a highly conserved SeC-containing module. An integrase frameshift fusion protein contains the N-terminal integrase DNA-binding domain and a potential ATP-binding "GKS" motif; it has significant similarities to several helicases, but no SeC codons. A potential frameshift fusion protein from env has one SeC codon, but not in a highly conserved position. SeC incorporation could extend the nef gene product by 33 residues through the C-terminal UGA codon without frameshifting, potentially leading to substantial SeC utilization in infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A basis for new approaches to the chemotherapy of AIDS: novel genes in HIV-1 potentially encode selenoproteins expressed by ribosomal frameshifting and termination suppression. 806 94

The analysis of the androgen receptor (AR) gene, mRNA, and protein in a subject with X-linked Reifenstein syndrome (partial androgen insensitivity) is reported. The presence of two mature AR transcripts in genital skin fibroblasts of the patient is established, and, by reverse transcriptase-PCR and RNase transcription analysis, the wild-type transcript and a transcript in which exon 3 sequences are absent without disruption of the translational reading frame are identified. Sequencing and hybridization analysis show a deletion of > 6 kb in intron 2 of the human AR gene, starting 18 bp upstream of exon 3. The deletion includes the putative branch-point sequence (BPS) but not the acceptor splice site on the intron 2/exon 3 boundary. The deletion of the putative intron 2 BPS results in 90% inhibition of wild-type splicing. The mutant transcript encodes an AR protein lacking the second zinc finger of the DNA-binding domain. Western/immunoblotting analysis is used to show that the mutant AR protein is expressed in genital skin fibroblasts of the patient. The residual 10% wild-type transcript can be the result of the use of a cryptic BPS located 63 bp upstream of the intron 2/exon 3 boundary of the mutant AR gene. The mutated AR protein has no transcription-activating potential and does not influence the transactivating properties of the wild-type AR, as tested in cotransfection studies. It is concluded that the partial androgen-insensitivity syndrome of this patient is the consequence of the limited amount of wild-type AR protein expressed in androgen target cells, resulting from the deletion of the intron 2 putative BPS.
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PMID:Differential splicing of human androgen receptor pre-mRNA in X-linked Reifenstein syndrome, because of a deletion involving a putative branch site. 812 58

Two forms of the transcription factor vHNF1 (HNF1 beta or LFB3) have been previously described, derived by alternative splicing from a common premessenger RNA, and have been called vHNF1-A and vHNF1-B. vHNF1 proteins share a homologous homeo-related DNA-binding domain with the HNF1 protein, initially characterized as a liver-restricted transcription factor, and bind to a similar sequence motif. Here we demonstrate that vHNF1-A is a stronger transactivator than vHNF1-B when assayed in transient transfections using two different promoters. vHNF1-A also binds DNA with a higher affinity suggesting that a region of the protein located immediately upstream of the homeodomain can modulate the protein/DNA interaction and transactivation. Both vHNF1 transcripts were found at a constant ratio in every tissue where vHNF1 expression could be detected, using a quantitative reverse transcriptase-polymerase chain reaction.
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PMID:The transactivation potential of variant hepatocyte nuclear factor 1 is modified by alternative splicing. 824 6

Analysis was made on the genomic structure, functions, and expression of the mouse ELP gene, which codes for the embryonal long terminal repeat binding protein. Extensive screening of the cDNA library of embryonal carcinoma cells (EC cells) identified four isoforms of ELP: ELP1 (the original ELP isolate), ELP2, ELP3, and Ad4BP/SF1. Analysis of the genomic sequences revealed that these ELP isoforms were generated by alternative promoter usage and differential splicing. The mRNAs of isoforms initiated at four transcription start sites distributed on three exons. Sequence analysis of the four isoforms identified three polypeptides. The N-terminal portion of ELP1 and ELP2 was longer than ELP3, and Ad4BP/SF1 by 77 aa. The DNA-binding domain and region II were shared by all four isoforms. The C-terminal portion shared by ELP2, ELP3, and Ad4BP/SF1 was 131 aa in length, and that specific to ELP1 was 57 aa in length. The ELP3 and Ad4BP/SF1 isoforms were identical for the coding sequence, but the two differed at the 5' noncoding region. Region II and III domains of nuclear receptors were thought to be involved in ligand-binding and transcriptional activation. ELP1, which lacked region III, functioned as a repressor. The isoforms carrying intact region II and region III functioned as transactivators. Expression of the four isoforms was studied in mouse tissues and in tissue culture cells by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Complex patterns of expression of these isoforms were observed in various tissues. All four ELP isoforms were expressed only in EC cells.
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PMID:Genomic organization and isoforms of the mouse ELP gene. 854 74

The pathogenesis of myxoid chondrosarcoma (CS) is poorly understood. A recurrent translocation, t(9;22) (q22;q12), has been recognized in CS, specifically in extraskeletal myxoid CS. Recently, this translocation has been shown to represent a rearrangement of the EWS gene at 22q12 with a novel gene at 9q22 designated CHN (or TEC). Sequence analysis suggests that CHN encodes a novel orphan nuclear receptor with a zinc finger DNA-binding domain. The structure of this gene fusion has been characterized in only a limited number of extraskeletal myxoid CSs and its presence in other types of CS has not been extensively examined. We studied 46 cases of CS (8 extraskeletal myxoid, 4 skeletal myxoid, 4 mesenchymal, and 30 other) for the EWS/CHN gene fusion by reverse transcriptase polymerase chain reaction, Southern blotting, and long-range DNA polymerase chain reaction. The EWS/CHN gene fusion was present in 6 of 8 extraskeletal myxoid CSs and was not detected in any of the remaining cases, including the 4 skeletal myxoid CSs. The negative findings in the latter cases suggest that skeletal myxoid CS is pathogenetically distinct from its extraskeletal counterpart. Notably, 2 cases of extraskeletal myxoid CS showed neither an EWS/CHN fusion transcript nor EWS/CHN genomic fusion nor EWS or CHN genomic rearrangement, suggesting genetic heterogeneity within extraskeletal myxoid CS. Finally, we also provide evidence for alternative splicing of the 3' end of the fusion transcript. Extraskeletal myxoid CS thus represents yet another sarcoma type containing a gene fusion involving EWS.
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PMID:Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. 906 Aug 41

Osteoblasts are established targets of estrogen action in bone. We screened 66 conditionally immortalized clonal human osteoblast cell lines for estrogen receptors (ERs) using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for ER alpha mRNA and transactivation of adenovirus-estrogen response element (ERE)-tk-luciferase by 17 beta-estradiol (17 beta-E2) for functional ER protein. One of these cell lines, termed HOB-03-CE6, was chosen for further characterization. The cells, which were conditionally immortalized with a temperature-sensitive SV40 large T antigen, proliferated at the permissive temperature (34 degrees C) but stopped dividing at the nonpermissive temperature (> or = 39 degrees C). Alkaline phosphatase activity and osteocalcin secretion were upregulated by 1 alpha, 25-dihydroxyvitamin D3 in a dose-dependent manner. The cells also expressed type I collagen and other bone matrix proteins, secreted a variety of growth factors and cytokines, formed mineralized nodules based on alizarin red-S and von Kossa histochemical staining, and responded to dexamethasone, all-trans retinoic acid, and transforming growth factor-beta 1. This cell line expressed 42-fold less ER message than MCF-7 human breast cancer cells, as determined by quantitative RT-PCR. However, adenovirus-ERE-tk-luciferase activity was upregulated three- to fivefold in these cells by 17 beta-E2 with an EC50 of 64 pM. Furthermore, this upregulation was suppressed by co-treatment with the anti-estrogen ICI-182, 780. Cytosolic extracts of these cells specifically bound [125I]-17 beta-E2 in a concentration-dependent manner with a Bmax of 2.7 fmoles/mg protein (approximately 1,200 ERs/cell) and a Kd of 0.2 nM. DNA gel-shift analysis using a [32P]-ERE demonstrated the presence of ERs in nuclear extracts of these cells. Moreover, binding of the extracts to this ERE was blocked by a monoclonal antibody to the human ER DNA-binding domain. We evaluated these cells for 14 of 20 reported endogenous responses to 17 beta-E2 in osteoblasts. Although most of these responses appeared to be unaffected by the steroid, 17 beta-E2 suppressed parathyroid hormone-induced cAMP production, as well as basal interleukin-6 mRNA expression; conversely, the steroid upregulated the steady-state expression of alkaline phosphatase message in these cells. In summary, we have identified a clonal, conditionally phenotypic, human osteoblast cell line that expresses functional ERs and exhibits endogenous responses to 17 beta-E2. This cell line will be a valuable in vitro model for exploring some of the molecular mechanisms of estrogen action in bone.
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PMID:Functional properties of a conditionally phenotypic, estrogen-responsive, human osteoblast cell line. 913 93

We found previously that long-chain fatty acids could inhibit eukaryotic DNA polymerase activities in vitro [1,2]. The purpose of the present study was to investigate the mode of this inhibition in greater detail. Among the C18 to C24 fatty acids examined, the strongest inhibitor was a C24 fatty acid, nervonic acid (NA), and the weakest was a C18 fatty acid, linoleic acid (LA). We analyzed the inhibitory effect of these two fatty acids and their modes of action. For DNA polymerase beta (pol. beta), NA acted by competing with both the substrate- and template-primer, but for DNA polymerase alpha (pol. alpha) or human immunodeficiency virus type 1 reverse transcriptase (HIV-1 reverse transcriptase or HIV-RT), NA acted non-competitively. NA-binding to pol. beta could be stopped with a non-ionic detergent, but the binding to pol. alpha or HIV-RT could not. The inhibition mode of LA showed the same characteristics, except that the minimum inhibitory dose of the longer chain was much lower. We also tested the effects of NA and LA using pol. beta and its proteolytic fragments, as described by Kumar et al. [3,4]. Both of the fatty acids were found to bind to the 8 kDa DNA-binding domain fragment, and to suppress binding to the template-primer DNA. We found that 10,000 times more of either fatty acid was required for it to bind to the 31 kDa catalytic domain or inhibit the DNA polymerase activity. The possible modes of inhibition by these long-chain fatty acids are discussed, based on the present findings.
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PMID:The inhibitory action of fatty acids on DNA polymerase beta. 936 79


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