Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of platinum(II) complexes on RNA polymerase II was studied. (D-Glucuronato)(1R,2R-cyclohexanediamine)platinum(II) nitrate (II-GHP) preferentially inhibited RNA synthesis in the presence of S-II, an essential component of eukaryotic transcription. When DNA was pretreated with I-GHP, its template activity decreased significantly, especially when assayed in the presence of S-II. The target of platinum(II) complexes is probably DNA. When DNA is modified, regulatory proteins of transcription, such as S-II, seem to lose their function preferentially on such a template, resulting in the inhibition of RNA synthesis.
Cancer Res 1983 Sep
PMID:Preferential inhibition of the activity of a stimulatory protein of eukaryotic transcription by platinum (II) complexes. 687 67

Events preceding glucocorticoid-induced growth inhibition and cytolysis were studied in CEM-C7 human leukaemic lymphoblasts. Inhibitory effects on uridine and thymidine incorporation and on RNA polymerase A activity preceded cell killing, and may relate to the arrest of the cells in the G1 phase of the cell cycle. An inhibitory effect on RNA polymerase B activity emerged later than the effect on RNA polymerase A; this action may reflect commitment to cell death. Cell death was not apparent within the first 24 hr of steroid treatment but thereafter was associated with extensive DNA fragmentation. The lethal action of dexamethasone in CEM-C7 cells was potentiated by 3-aminobenzamide, an inhibitor of poly(ADP-ribose)polymerase.
Eur J Cancer Clin Oncol 1982 Nov
PMID:Temporal relationships between inhibitory effects of glucocorticoids on cells of the CEM-C7 human leukaemic lymphoblast cell line. 689 52

Activity levels of DNA-dependent RNA polymerase I (Pol I; ribonucleoside triphosphate: RNA ribonucleotidyl transferase, E.C. 2.7.7.6, eucaryotic type I) have been compared in five transplantable murine hepatomas and livers of three inbred mouse host strains. Three tumors (H6, H4 and H134) contained about 350-450 units of Pol I activity/g of tissue. Two hepatomas (H129 and BW7756) contained about 120-150 units of activity/g of tissue. Livers contained about 100-150 units/g of tissue. Chromatographic comparisons revealed that hepatoma Pol I is slightly less anionic than the liver enzyme. Thermal denaturation studies were carried out using Pol I partially purified from a high-activity line hepatoma (H6), a low-activity line hepatoma (H129) and livers of the appropriate host strains. Pol I from H6 tumors was denatured at 40 degrees C with a half-time of 2 min. The enzyme from H129 tumors and host livers was denaturated with a half-time of 7 min. These data indicate that hepatoma H6 expressed a structural variant of Pol I. This is the first Pol I variant ever reported.
Cancer Biochem Biophys 1981
PMID:DNA-dependent RNA polymerase I from hepatomas: comparison of activity levels and properties. 724 19

DNA isolated from cell nuclei by intensive deproteinization with chloroform/isoamyl alcohol and phenol extractons contains a low molecular weight peptidic fraction in a quantity of about 20 micrograms/mg DNA. These peptides were characterized by chromatography on CM-Sephadex, Sephadex G-25, high performance liquid chromatography on microBondapak C18 and amino acid composition. The peptides control transcription in a reconstituted cell-free system with prokaryotic and eukaryotic RNA polymerase and stabilize the structure of double stranded DNA, while increasing its melting point. Their level is markedly decreased (by about 40%) in DNA prepared from tumor cells as compared to normal cell DNA. Transcriptional studies showed only a slightly increased template activity of DNA extracted at pH 9.5 versus DNA extracted at pH 6.0 for DNA preparations from tumor cells. However, there was a marked increase in template activity for DNA preparations treated at pH 9.5 from normal cells--232%, 124%, 97% and 78% for rat liver, mouse liver, mouse thymus and fibroblast L-929 cells, respectively. Also there was no difference in the melting point between these two preparations of DNA from tumor cells; normal cell DNA preparations showed increased melting point of preparations treated at pH 6.5. The data obtained indicate that the loss of low molecular weight peptides from tumor DNA during carcinogenesis is responsible for uncontrolled gene expression observed in cancer.
 ...
PMID:Low molecular weight peptidic fraction in the chromatin from normal and cancer cells: control of transcription. 741 71

Peptides of melanosomal proteins have recently been shown to be recognized in an HLA-restricted mode by specific cytolytic T lymphocytes in melanoma patients. Dendritic antigen-presenting cells (DC) are considered to be the most effective stimulators of T cell responses, and the use of these cells has therefore been proposed to generate therapeutic responses to tumor antigens in cancer patients. We, therefore, generated DC from peripheral blood of normal donors in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. Flow cytometric analysis of the cells during a 2-week culture revealed a loss of CD14 and CD34 expression, a concomittent increase of CD1a, CD11a,b and c, CD44, CD45, CD54, HLA-class I and II, and intermediate levels of CD26, CD80 and CD86. Cultured DC stimulated proliferation of allogeneic T cells and induced a marked, up to 20-fold, stimulation of T cell proliferation after pulsing with tetanus toxoid. To achieve independence of already-identified antigenic peptides presented in HLA class I-restricted fashion, which limits the general applicability of such peptides for vaccination of melanoma patients, we tested whether DC are transfectable with eukaryotic expression plasmids. DC transfected with two reporter genes (CAT, beta-galactosidase) using a liposome-based transfection technique, exhibited only low levels of enzymatically active proteins, but were able to degrade rapidly intracellular proteins and to process peptides efficiently. Chloramphenicol acetyltransferase as well as tyrosinase mRNA were detectable after transfection by reverse-transcriptase-polymerase chain reaction, and enzyme activities became measurable. Furthermore, DC transfected with the tyrosinase gene were able to induce specific T cell activation in vitro, indicating appropriate peptide processing and presentation in DC after transfection. These data suggest new approaches to future tumor vaccination strategies.
 ...
PMID:Dendritic cells generated from peripheral blood transfected with human tyrosinase induce specific T cell activation. 748 49

Fli-1, an ets related gene, was found to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have shown previously that the Fli-1 gene codes for a sequence specific transcriptional activator which contains two autonomous transcriptional activation domains, one at the amino terminal region and the other at the carboxy terminal region. Recently human Fli-1 gene was shown to be involved in Ewing's sarcoma and related subtypes of primitive neuroectodermal tumors which share t(11;22) (q24;q12) chromosome translocation. In these tumors the carboxyl terminal region of Fli-1 was found to be fused with the amino terminal region of a putative RNA binding protein, EWS. Because part of the amino terminal transcriptional activation domain of Fli-1 was replaced with the amino terminal domain of the EWS (NTD-EWS) which shares homology with RNA polymerase II, it was speculated that NTD-EWS may interfere with RNA pol II function. Alternatively, NTD-EWS could also contribute to the transcriptional activation function of EWS/Fli-1 chimeric protein by providing either a modulatory/regulatory domain or a novel transcriptional activation domain. Here we show that EWS/Fli-1 chimeric protein functions as a transcriptional activator. Deletion analysis reveals that the EWS domain functions as a modulatory/regulatory domain for the transcriptional activation properties of the carboxy terminal transcriptional activation domain of EWS/Fli-1. We therefore propose that replacement of the amino terminal transcriptional activation domain of the Fli-1 protein with the regulatory domain of NTD-EWS results in the activation of the carboxy terminal transcriptional activation domain of Fli-1 which may be the molecular mechanism involved in these human tumors.
Cancer Res 1993 Dec 15
PMID:EWS/Fli-1 chimeric protein is a transcriptional activator. 750 13

Recently, it has been demonstrated that nitrogen mustard-induced N-alkylpurines are excised rapidly from actively transcribing genes, while they persist longer in noncoding regions and in the genome overall. It was suggested that transcriptional activity is implicated as a regulatory element in the efficient removal of lesions. By treating cells or not with the transcription inhibitor alpha-amanitin, we have explored whether ongoing activity of RNA polymerase II was coordinately related to proficient repair of nitrogen mustard-induced alkylation products in the actively transcribed dihydrofolate reductase gene in the Chinese hamster ovary B11 cells. Nuclear run-off transcription analysis verified that alpha-amanitin completely and selectively inhibited transcription by RNA polymerase II. At the drug exposure examined, nitrogen mustard induced DNA damage capable of a complete transcription termination in the RNA polymerase II-transcribed dihydrofolate reductase gene and reduced 28S rDNA transcription by a factor of 7.9. The transcription activity did partially recover following reincubation in drug-free medium; this recovery was about 34 and 76% of ribosomal 28S gene transcripts and dihydrofolate reductase gene transcripts, respectively, after 6 h of repair incubation. alpha-Amanitin significantly inhibited the removal of nitrogen mustard-induced N-alkylpurines in the 5'-half of the essential, constitutively active dihydrofolate reductase gene, while no effect of alpha-amanitin was observed on the lesion removal from a noncoding region 3'-flanking to the gene and from the genome overall. In the actively transcribed gene region, about 77% of N-alkylpurines were removed 21 h following drug exposure of cells not treated with alpha-amanitin and about 47% in 21 h in alpha-amanitin treated cells. The global semiconservative replication seemed unaffected by the alpha-amanitin treatment. From these results we suggest that gene-specific repair of nitrogen mustard-induced N-alkylpurines is dependent on ongoing activity of the transcribing RNA polymerase II. The findings are discussed in terms of the current ideas about the mechanism of preferential DNA repair.
Cancer Res 1994 Jan 01
PMID:Ongoing activity of RNA polymerase II confers preferential repair of nitrogen mustard-induced N-alkylpurines in the hamster dihydrofolate reductase gene. 750 96

The present study was undertaken to define the gene(s) of importance on the long arm of chromosome 18 (chromosome 18q) in endometrial carcinomas. We analyzed loss of heterozygosity (LOH) at 3 loci on chromosome 18q and DCC gene expression by the reverse-transcriptase/polymerase chain reaction (RT-PCR) method. Among 61 tumors that were informative, 16 (26%), estimated to be a minimum number, showed allelic losses at one or more chromosome 18q loci. Deletions in these tumors possibly involved the region within or near the chromosome 18q 21.3 band where the DCC gene was localized. Moreover, the incidence of altered DCC mRNA expression was high in these tumors. Appropriate transcription was lost in 5 of 7 (71%) carcinoma cell lines in addition to 14 of 28 (50%) surgically resected tumors. Histopathological differentiation and clinical stage of disease were not related to LOH frequency or to DCC mRNA expression. These results suggest that the target for allelic loss on chromosome 18q seen in endometrial carcinomas is the DCC gene, and that inactivation of this gene may be critical for the development of most endometrial carcinomas.
Int J Cancer 1994 May 15
PMID:DCC gene alteration in human endometrial carcinomas. 751 50

During mitosis, ribosomal genes are associated with a set of silver-stained nucleolar proteins designated Ag-nucleolar organizer region (NOR) proteins. The amount of Ag-NOR protein, estimated during interphase, may be used as marker of cell proliferation with a prognostic value for several human cancers. Our objective was to identify the Ag-NOR proteins in human transformed cell lines at specific phases of the cell cycle and in a hamster cell line that serves as model for active ribosomal transcription. During interphase, the major Ag-NOR proteins in both human and hamster cells were nucleolin and protein B23 and also proteins of 42, 40, and 29 kDa, which accounted for a small amount of the silver stain. The pIs of these proteins were between 4.5 and 5.6. During mitosis, the Ag-NOR proteins were either solubilized in the cytoplasm, distributed around the chromosomes, or associated with the ribosomal genes, i.e., in the NORs. The major Ag-NOR proteins associated with the ribosomal genes were the largest RNA polymerase I subunit, the 135-kDa NOR protein, the UBF transcription factor, and a 50-kDa protein. Less than 5% of the total nucleolin remained associated with ribosomal genes during mitosis. Using the purified RNA polymerase I complex from yeast, we demonstrate that the 190-, 43-, and 34.5-kDa subunits are Ag-NOR proteins in this species. This study demonstrates that the major Ag-NOR proteins in nucleoli during interphase are not the same as those associated with the ribosomal genes during mitosis. We conclude that the prognostic test for human cancer cell proliferation is largely based on the amount of the nucleolar proteins, nucleolin, and protein B23, which are not directly involved in ribosomal gene transcription. In contrast, the evaluation of active NORs in karyotypes during mitosis is based on the presence of some proteins of the ribosomal gene transcription machinery.
 ...
PMID:Identification of Ag-NOR proteins, markers of proliferation related to ribosomal gene activity. 752 52

Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric transcripts can be readily detected by reversed transcriptase polymerase chain reaction (RT-PCR). This approach led to the identification of a number of different exon combinations at the junction site of coding sequences. The physiological consequences of the observed variability in the hinge region of EWS chimaeric proteins are not known. We have analysed tumour-derived material from 30 ET patients with well-documented clinical course (18 with localised and 12 with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%). In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7 (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in one case each. In the last tumour, the presence of at least four additional splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8 and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations 7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and were more abundant in tumours affecting the long bones (9 versus 0), whereas in central axis tumours and metastatic disease there was only little difference in the frequency of the two types. So far, no correlations between different chimaeric EWS transcripts and any other clinical parameters have been identified.
Br J Cancer 1994 Nov
PMID:Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. 752 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>