Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NH2-terminal amino acid sequence of Moloney murine leukemia virus reverse transcriptase was determined to be Thr-Leu-Asn-Ile-Glu-Asp-Glu-Tyr-Arg-Leu-His-Glu-. The comparison of the amino acid analysis data obtained after carboxypeptidase Y digestion with the published nucleotide sequence (T. M. Shinnick, R. A. Lerner, and J. G. Sutcliffe, Nature (London) 293, 543-548, 1981) led to the conclusion that the COOH-terminus is Leu coded by CTC in nucleotide positions 4608-4610, and the tentative COOH-terminal sequence is Pro-Asp-Thr-Ser-Thr-Leu-Leu-OH. In light of these and previously reported results the complexity and map order of the pol gene are discussed.
 ...
PMID:Amino- and carboxyl-terminal sequence of Moloney murine leukemia virus reverse transcriptase. 241 14

A COS-like monkey kidney cell line stably transfected with the plasmids pCMVgagpol-rre-r with the gag and pol genes, and pCMV rev with the rev gene of HIV-1 derived from the cDNA clone BH10, was used as a model for assessing the effectiveness of antisense (AS) constructs, A 20-mer oligodeoxyribonucleotide (oligo) phosphorothioate sequence (5'-CCG CCC CTC GCC TCT TGC CG) complementary to a portion of the 5'-long terminal repeat (5'-LTR) of the HIV-1 genome was tested for its inhibitory effects on the biologically important processes of HIV-1 replication and proliferation. We observed a concentration-dependent inhibition of HIV protein synthesis. Desitometric analysis of data from Western blot analysis showed sequence-specific and concentration-dependent oligo inhibition of p24 viral core antigen formation in the low-microM range. When lipofectin was used as a delivery vehicle, a markedly increased potentiation of the AS activity of the sequence was observed at a lower concentration (0.1 microM), following a 24-h preincubation. The AS construct specifically inhibited intracellular p24 production in chronically HIV-1-infected cells of lymphoid origin (H9/IIIB cells) by 95%, resulting in a 15-fold inhibitory effect relative to a similar sequence thiolated at only seven single-base positions. A concentration-dependent attenuation in the reverse transcriptase activity and a reduction in viral p24 level was observed in the culture supernatant of AS-pretreated HIV-1-infected phytohemagglutinin A-stimulated human cord blood mononuclear cells. Incubation of a HIV-1-infected lymphoid cell line with AS sequence resulted in a marked reduction in syncytium formation, and therefore protected cells from the cytopathic effects of the virus. Furthermore, the AS oligo did not appear to be cytotoxic in cell growth rate and colony-forming ability assays. The AS oligo described in this report is a useful new tool for the molecular analysis of HIV-1 gene expression and proliferation, and may have potential as a therapeutic agent.
 ...
PMID:Antiviral activity and protection of cells against human immunodeficiency virus type-1 using an antisense oligodeoxyribonucleotide phosphorothioate complementary to the 5'-LTR region of the viral genome. 854 66

Arsenic trioxide (As2O3) has been used as an effective chemotherapy agent for some human cancer, such as acute promyelocytic leukemia. We have demonstrated that low level of As2O3 relatively selectively inhibited growth of the solid tumor MGC-803 cells by triggering apoptosis. In this study, we found PIG11, a p53-induced gene, was upregulated markedly by As2O3 using the technique of differential display reverse transcriptase PCR (DDRT-PCR). Addition of anti-PIG11 phosphorothioated oligonucleotide (5'-GGC CGC CAT CTT CTC CTC-3') before As2O3 treatment, abolished the transient increase in PIG11 gene expression. Furthermore, it significantly inhibited the As2O3-induced apoptosis of MGC-803 cells, but had no effect in addition of missense (5'-GAG GAG AAG ATG GCG GCC-3') phosphorothioated oligonucleotides. These results suggest that PIG11, as a downstream target of p53, is involved in apoptosis of MGC-803 cells.
 ...
PMID:P53-induced gene 11 (PIG11) involved in arsenic trioxide-induced apoptosis in human gastric cancer MGC-803 cells. 1288 91

We have compared nucleotide substitutions and polymorphisms at codons known to confer drug resistance in subtype B strains of human immunodeficiency virus type 1 (HIV-1) with similar substitutions in viruses of other subtypes. Genotypic analysis was performed on viruses from untreated individuals. Nucleotide and amino acid diversity at resistance sites was compared with a consensus subtype B reference virus. Among patients with non-subtype B infections, polymorphisms relative to subtype B were observed at codon 10 in protease (PR). These included silent substitutions (CTC-->CTT, CTA, TTA) and an amino acid mutation, L10I. Subtype A viruses possessed a V179I substitution in reverse transcriptase (RT). Subtype G viruses were identified by silent substitutions at codon 181 in RT (TAT-->TAC). Similarly, subtype A/G viruses were identified by a substitution at position 67 in RT (GAC-->GAT). Subtype C was distinguished by silent substitutions at codons 106 (GTA-->GTG) and 219 (AAA-->AAG) in RT and codon 48 (GGG-->GGA) in PR. Variations relative to subtype B were seen at RT position 215 (ACC-->ACT) for subtypes A and A/E. These substitutions and polymorphisms reflect different patterns of codon usage among viruses of different subtypes. However, the existence of different subtypes may only rarely affect patterns of drug resistance-associated mutations.
 ...
PMID:Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. 1527 11

Although rare, sarcomas represent a source of significant morbidity and mortality with nearly one reported death for every two new diagnoses. The detection and surveillance of circulating tumor cells (or CTCs) has been found to have significant clinical utility in epithelial malignancies, such as carcinoma of the colon, breast and prostate. Here, we summarize what is known regarding CTCs in sarcomas. Although still in its relative infancy, the detection of CTCs in sarcoma patients may help to diagnose and predict recurrence or metastasis as well as improve the overall management of sarcoma patients. CTCs are most often detected via reverse transcriptase polymerase chain reaction or antibody-based detection of cell surface proteins, including flow cytometry. Samples may be obtained from either peripheral blood or bone marrow. CTC detection in translocation sarcomas is perhaps most promising, as a recurrent abnormal gene fusion product can be detected in involved individuals but not in the normal patient. Studies in Ewing's sarcoma/peripheral neuroectodermal tumor, synovial sarcoma and alveolar soft part sarcoma have confirmed the feasibility of this approach. Other investigators have turned toward detection of more universal markers of sarcomas, such as the pan-mesenchymal marker Vimentin. In the case of osteosarcoma, more specific markers of osteogenic differentiation (Type I Collagen) have been utilized. In summary, although in its relative nascency, the use of CTC detection for the management of sarcoma patients shows initial promise.
...
PMID:Circulating tumor cells in sarcomas: a brief review. 2549 Nov 43