Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of human cells by adenovirus results in multiple alterations of host gene expression. To examine the effects of viral infection on the expression of a single gene, a line of human cells was developed which is resistant to growth in methotrexate and which contains amplified RNA and protein specific for dihydrofolate reductase (DHFR). Cytogenetic evidence indicated the presence of amplified DNA. Adenovirus infection of these cells caused an induction and subsequent decline in the synthesis of DHFR protein. The maximum DHFR induction occurred 16 to 19 h after infection and reached a level 2.5-fold greater than that observed in uninfected cells. Induction of DHFR protein synthesis was accompanied by concomitant increases in the level of steady-state DHFR-specific cytoplasmic RNA. The relative rate of DHFR mRNA production (i.e., the appearance of DHFR-specific mRNA sequences in the cytoplasm) also increased 2.5-fold during induction. Later in infection, the relative rate of DHFR protein synthesis declined, reaching a level below that observed in uninfected cells. This decline was accompanied by a similar decline in the steady-state levels of DHFR RNA and in the relative rate of synthesis of DHFR mRNA. These data suggest that adenovirus infection controls DHFR gene expression by increasing and subsequently decreasing the relative rate at which DHFR-specific mRNA sequences appear in the cytoplasm and enter the pool of mRNA available for translation.
Mol Cell Biol 1983 May
PMID:Control of cellular gene expression during adenovirus infection: induction and shut-off of dihydrofolate reductase gene expression by adenovirus type 2. 686 43

We have purified to homogeneity and characterized a 55,000-dalton rat cell membrane glycoprotein, gp55. This protein was originally identified in preparations of a defective pseudotype of the Kirsten sarcoma virus and shown to be present in several rodent retrovirus particles. The gp55 was purified from this defective virus by concanavalin A and heparin affinity chromatography, as well as by preparative sodium dodecyl sulfate-gel electrophoresis. Both preparations displayed similar purity and antigenic characteristics. The 125I-labeled gp55 was precipitated by antisera against rodent retroviruses, but not by monospecific antisera against purified type C virus structural proteins, thus indicating that gp55 was retrovirus associated, but unrelated to known retrovirus structural proteins. Competition radioimmunoassay with an anti-rat virus serum which recognized rodent group-specific antigens on gp55 indicated: the presence of gp55 antigens in 15 rodent cell lines, but not 10 nonrodent cell lines; no effect of viral infection or cell transformation on the amount of gp55 expressed; up to 100-fold increases in the concentration of the gp55 antigens in nine rodent retroviruses, but not in five nonrodent viruses, as compared to cells; the presence of gp55 in rodent sera, especially of the NZB mouse, where anti-gp55 antibody was also detected; a lymphoid and epithelial tissue distribution of gp55 in rats and mice. Additional competition radioimmunoassays with a broad-reacting antivirus serum also detected the presence of gp55 in nonrodent, mink, and human cells and thus distinguished rat type, rodent group, and interspecies antigenic determinants on gp55. In conclusion, gp55 is a cell membrane glycoprotein associated in high concentration with retroviruses.
Mol Cell Biol 1981 Feb
PMID:55,000-dalton, retrovirus-associated, cell membrane glycoprotein: purification and quantitative measurements of expression in viruses, cells, and tissues. 696 96

Various cases of DNA (RNA) transfer through membranes of living cells are reviewed. They are classified into two major categories: those which occur in Nature (natural transfer) and those imposed by various physical and chemical treatments of cells (induced transfer). Among the examples of natural transfer surveyed are the transfer during bacterial conjugation, genetic transformation, viral infection of bacteria, and nuclear membrane trafficking. Consideration of the induced transfer is focused on the two methods most widely used at present to introduce foreign genetic information into pro- and eukaryotic cells: Ca2+ (and some other divalent cations)-induced and calcium phosphate-induced transfer, and transfer during electroporation of cells. Emphasis is made on the underlying mechanisms of transfer, or rather on what is currently known about them. Energetic aspects of transfer are also discussed and different tentative models of transfer are presented.
Prog Biophys Mol Biol 1994
PMID:Nucleic acid transfer through cell membranes: towards the underlying mechanisms. 752 11

There now appears to be evidence to support the view that the type I IFNs are naturally produced negative regulators of growth that also modify cell differentiation. Consistent with this, it appears that the ability to produce and respond to IFN is suppressed in early embryonic development when cell proliferation and differentiation are essential. In the later stages of fetal development, IFN production is de-repressed, and cells show increased sensitivity to IFN, which may be important in regulating cell proliferation and/or differentiation processes or the interaction between fetal and maternal tissues. Interestingly, the IFN system can also be suppressed in disease states such as the development of tumours or in the establishment of a (chronic) viral infection. Therefore, understanding the developmental regulation of the IFN system may be important to understanding and controlling the IFN system in disease. More extensive studies of the developmental stage and tissue-specific expression of type I IFNs and their receptors are necessary, as well as more direct in vivo experiments to further elucidate the role of the IFN system in reproduction and development.
Mol Reprod Dev 1994 Oct
PMID:Role of interferons in the regulation of cell proliferation, differentiation, and development. 753 16

Stable transfer of genetic information into neurons is a powerful strategy to elucidate specific mechanisms of neurophysiology and to develop therapies for neurological disorders. To evaluate the optimal parameters for efficient gene delivery of defective herpes simplex virus type one (HSV-1) vectors into a specific brain region, an HSV-1 vector expressing E. coli beta-galactosidase was used to infect organotypic cultures of hippocampal slices. beta-Galactosidase was expressed as early as 2 h after infection in a dose-dependent manner as measured on immunoblots, and reached a maximum level after approximately 35 h. Expression of the RNA and the antigen was still evident after the longest time sampled (11-12 days), whereas no beta-galactosidase was ever detected in cultured slices infected with a control virus lacking the reporter gene. Hippocampal cells expressing the reporter gene outlined the contour of the neuronal cell body layers in fields CA3 and dentate gyrus; such correspondence was less evident in field CA1. Anatomical, morphological, and immunohistochemical criteria also confirmed that the majority of these infected cells were neurons. beta-Galactosidase was also detected in the somata and processes of infected interneurons. Tests for synaptic pathology associated with virus infection showed no changes in pre- and postsynaptic markers.
Brain Res Mol Brain Res 1994 Oct
PMID:Rapid and stable gene expression in hippocampal slice cultures from a defective HSV-1 vector. 753 3

The imidazoquinolineamine derivative 1-(2-methyl propyl)-1H-imidazole [4,5-c]quinoline-4-amine (imiquimod) has been shown to induce alpha interferon (IFN-alpha) synthesis both in vivo and in peripheral blood mononuclear cells in vitro. In this study, we show that, in these cells, imiquimod induces expression of several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. Expression of all these genes was transient, independent of cellular protein synthesis, and inhibited in the presence of tyrosine kinase and protein kinase C inhibitors. Infection with Sendai virus led to expression of a similar set of cytokine genes and several of the IFNA genes. Imiquimod stimulates binding of several induction-specific nuclear complexes: (i) the NF-kappa B-specific complexes binding to the kappa B enhancer present in the promoters of all cytokine genes, but not in IFNA genes, and (ii) the complex(es) binding to the A4F1 site, 5'-GTAAAGAAAGT-3', conserved in the inducible element of IFNA genes. These results indicate that imiquimod, similar to viral infection, stimulates expression of a large number of cytokine genes, including IFN-alpha/beta, and that the signal transduction pathway induced by both of these stimuli requires tyrosine kinase and protein kinase activity.
Mol Cell Biol 1995 Apr
PMID:Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. 753 79

Proliferation of aortic smooth muscle cells (SMCs), an important feature of atherosclerosis, occurs in the early stage of the disease in Japanese quail when fed an atherogenic diet. Quail aortic SMCs were isolated from a total of 32 quail and cultured in Eagle's minimum essential medium supplemented with 10% bovine fetal serum. Studies were carried out to characterize the cells in vitro. They grew actively in the early passages, but began to develop cytopathic changes after 3-4 passages and eventually cell death. The pathobiology had similarities to virus infected cells. Whole-mount electron microscopic examination detected virus-like particles in the cultured cells. All cell lines tested were positive for viral infection as screened by DNA dot blot hybridization using a genomic library of Marek's disease herpesvirus as a probe. However, the attempt to isolate the virus was unsuccessful. In summary, these cell lines are believed to be infected by a putative quail herpesvirus. Results of this in vitro cellular study support previous findings that the atherosclerosis susceptible quail are latently infected in vivo. Future studies will be needed to determine whether the virus plays a role in the pathogenesis of atherosclerosis in this animal model.
Exp Mol Pathol 1994 Dec
PMID:Culture characterization and viral infection of aortic smooth muscle cells from Japanese quail susceptible to atherosclerosis. 760 Dec 71

Human immunodeficiency virus type 1 (HIV-1) pre-mRNA splicing is regulated in order to maintain pools of unspliced and partially spliced viral RNAs as well as the appropriate levels of multiply spliced mRNAs during virus infection. We have previously described an element in tat exon 2 that negatively regulates splicing at the upstream tat 3' splice site 3 (B. A. Amendt, D. Hesslein, L.-J. Chang, and C. M. Stoltzfus, Mol. Cell. Biol. 14:3960-3970, 1994). In this study, we further defined the element to a 20-nucleotide (nt) region which spans the C-terminal vpr and N-terminal tat coding sequences. By analogy with exon splicing enhancer (ESE) elements, we have termed this element an exon splicing silencer (ESS). We show evidence for another negative cis-acting region within tat-rev exon 3 of HIV-1 RNA that has sequence motifs in common with a 20-nt ESS element in tat exon 2. This sequence is juxtaposed to a purine-rich ESE element to form a bipartite element regulating splicing at the upstream tat-rev 3' splice site. Inhibition of the splicing of substrates containing the ESS element in tat exon 2 occurs at an early stage of spliceosome assembly. The inhibition of splicing mediated by the ESS can be specifically abrogated by the addition of competitor RNA. Our results suggest that HIV-1 RNA splicing is regulated by cellular factors that bind to positive and negative cis elements in tat exon 2 and tat-rev exon 3.
Mol Cell Biol 1995 Aug
PMID:Presence of exon splicing silencers within human immunodeficiency virus type 1 tat exon 2 and tat-rev exon 3: evidence for inhibition mediated by cellular factors. 756

Respiratory syncytial virus (RSV) is an important respiratory pathogen that preferentially infects epithelial cells in the airway, and causes a local inflammatory response. Although it has been previously demonstrated that RSV-infected airway epithelial produce cytokines, including interleukin-8 (IL-8), which contributes to the inflammatory response, the regulation of this effect of RSV is unknown. To further characterize the mechanisms by which RSV infection triggers release of IL-8, we first exposed cultured A549 cells to RSV, and measured IL-8 release via enzyme-linked immunosorbent assays (ELISA), and IL-8 messenger RNA (mRNA) induction via Northern blot analysis. We observed a dose- and time-dependent release of IL-8 in response to RSV. The optimal dose of RSV was 10(4) TCID50/ml, and maximal release of IL-8 was measured at 72 to 96 h after infection. RSV induced a biphasic (early and late) increase in IL-8 mRNA. The early phase was independent of viral infection, whereas the more pronounced late phase required the presence of live virus and infection of the epithelium. Partial (< 50%) cytopathic effects were noted at 48 h and progressed to 75% at 96 h. The monolayer was still intact at 96 h. Inhibitors of nitric oxide, including NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and aminoguanidine had no effect on IL-8 release or IL-8 mRNA induction. We did, however, demonstrate a dose-dependent decrease in IL-8 release and IL-8 mRNA induction in RSV-infected epithelial treated with the antioxidants dimethyl sulfoxide (DMSO) or 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Peak effects were noted at a concentration of 2% DMSO and 50 microM DMPO. The antioxidants did not inhibit viral replication or infection. This data suggest that RSV-induced IL-8 production in airway epithelium is mediated via changes in oxidant tone. The data also suggest a potential therapeutic role for antioxidants in RSV infections.
Am J Respir Cell Mol Biol 1995 Aug
PMID:Oxidant tone regulates IL-8 production in epithelium infected with respiratory syncytial virus. 762 91

The polyomavirus late polyadenylation signal is used inefficiently during the late phase of a productive viral infection. Inefficient polyadenylation serves an important purpose for viral propagation, as it allows a splicing event that stabilizes late transcripts (G. R. Adami, C. W. Marlor, N. L. Barrett, and G. G. Carmichale, J. Virol. 63:85-93, 1989; R. P. Hyde-DeRuyscher and G. G. Carmichael, J. Virol. 64:5823-5832, 1990). We have recently shown that late-strand readthrough transcripts serve as natural antisense molecules to downregulate early-strand RNA levels at late times in infection (Z. Liu, D. B. Batt, and G. G. Carmichael, Proc. Natl. Acad. Sci. USA 91:4258-4262, 1994). Thus, poor polyadenylation contributes to the early-late switch by allowing the formation of more stable late RNAs and by forming antisense RNA to early RNAs. The importance of late poly(A) site inefficiency in the viral life cycle has prompted us to map the cis elements of this site. Since the polyomavirus late site proved a poor substrate for in vitro polyadenylation, we used an in vivo assay which allowed us to map the cis sequences required for its function. In this assay, various fragments containing the AAUAAA and different surrounding sequences were placed 1.4 kb upstream of a second, wild-type signal. The second signal served to stabilize transcripts that are not processed at the upstream site, allowing accurate quantitation of relative poly(A) site use by an RNase protection assay. Processing was primary at the upstream site when a large fragment surrounding the poly(A) signal (50 nucleotides [nt] upstream and 90 nt downstream) was tested in this assay, demonstrating that this fragment contains the essential cis elements. Deletion analysis of this fragment revealed that most but not all upstream sequences can be removed with little effect on polyadenylation efficiency, indicating the absence of a strong stimulatory upstream element. Deletion of all but 25 nt downstream of the AAUAAA reduced polyadenylation activity only by half, demonstrating that processing can occur at this site despite the lack of downstream sequences. Thus, the core cis element for polyadenylation is quite small, with most important cis-acting elements lying within 19 nt upstream and 25 nt downstream of the AAUAAA sequence. This core contains the AAUAAA hexanucleotide, an upstream A/U-rich element, and three identical repeats of a 6-nt sequence, UAUUCA. Polyadenylation was eliminated or greatly reduced when either the AAUAAA or the three repeats were mutated.
Mol Cell Biol 1995 Sep
PMID:Characterization of the polyomavirus late polyadenylation signal. 765 95


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