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Query: UNIPROT:P06889 (Mol)
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Infection of PC12 cells with Japanese encephalitis (JE) virus caused marked proliferation of the protein secretory system. Accordingly, in this study the morphogenesis of the secretory organelles, i.e., rough endoplasmic reticulum (RER) and the Golgi apparatus, in JE virus-infected PC12 cells was analyzed by electron microscopical observation. Starting 24 h postinoculation (p.i.), a structure that represented nascent RER appeared in the cytoplasm in the form of rows of ribosomes which surrounded membrane-unbounded, electron-lucent lacunae in a reticular, honey-comb pattern (reticular RER). Although the reticular RER lacked membrane components, its lacunae contained progeny virions, indicating that the rows of ribosomes synthesized the viral proteins and discharged them into the lacunae for the viral assembly. The reticular RER apparently transformed into the familiar lamellar RER during the RER morphogenesis as the lacunae coalesced to form flat cisternae and RER membrane assembled to border the cisternae. These findings indicated that the proliferating RER was the site of not only active protein synthesis but also active membrane biogenesis. The proliferating RER released a large number of membrane vesicles including virion-carrying vesicles into the cytoplasm. These vesicles congregated in the juxtanuclear region, especially around the centrioles, and fused to existing Golgi complexes for enlargement or fused among themselves to form new Golgi complexes. The present study, therefore, indicated that (a) nascent RER was formed by polysomes that arranged themselves in rows of ribosomes without participation of a preexisting membrane framework of endoplasmic reticulum (ER), (b) membrane components of RER were assembled de novo within the structure during the RER morphogenesis, and (c) RER released membrane vesicles that moved to the Golgi apparatus and contributed to the morphogenesis of the Golgi apparatus. Possible causative mechanisms involved in the proliferation of the secretory system in JE virus-infected PC12 cells are discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Morphogenesis of the protein secretory system in PC12 cells infected with Japanese encephalitis virus. 828 19

In an effort to correlate biochemical characteristics of the beta-adrenergic receptor complex with myocardial function, mouse myocardial GTP-binding proteins, specifically substrates for pertussis toxin (PT), were analysed with regard to the influence of infection with Trypanosoma cruzi, the causative agent of Chagas' cardiomyopathy. Infection was found to decrease in a non-uniform manner the magnitude of ADP-ribosylation in the PT substrates. High detergent concentrations attenuated the infection-associated decrease in PT-dependent ADP-ribosylation. Infection also altered the kinetics of the PT-dependent ADP-ribosylation reaction from a time course wherein maximal PT-dependent ADP-ribosylation occurred after 12 h incubation in control animals to one in which maximal PT-dependent ADP-ribosylation occurred after 3 h incubation and thereafter declined. Immunochemical analysis of the PT-substrates revealed an infection-associated decrease in alpha i1, alpha o, an increase in alpha i2 and no change in alpha i3. Verapamil treatment, which prevents the clinical consequences of infection, did not influence any of the infection-associated changes in PT-dependent ADP-ribosylation of GTP-binding protein substrates or their immunochemical properties. Complementary studies using isolated rat neonatal cardiocytes infected with the parasite further substantiated the finding that the infection-associated decrease in PT-dependent ADP-ribosylation and the associated change in the kinetics of the reaction were properties uniquely associated with the presence of the parasite.
J Mol Cell Cardiol 1993 Nov
PMID:Evidence that myocardial pertussis toxin substrates are uniquely altered in acute murine Chagas' disease in a manner unrelated to myocardial dysfunction. 830 65

In vivo studies of Friend virus erythroleukemia have implied that proviral integrations adjacent to the gene for the Ets-related transcription factor PU.1 may inhibit the commitment of erythroblasts to differentiate and cause their capability for indefinite transplantation (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 62:4129-4135, 1988; R. Paul, S. Schuetze, S. L. Kozak, C. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test this hypothesis, we ligated PU.1 cDNA into a retroviral vector and studied its effects on cultured cells. Infection of fibroblasts with PU.1-encoding retrovirus resulted in PU.1 synthesis followed by nuclear pyknosis, cell rounding, and degeneration. In contrast, in long-term bone marrow cultures, erythroblasts were efficiently and rapidly immortalized. The resulting cell lines were polyclonal populations that contained PU.1, were morphologically blast-like, required erythropoietin and bone marrow stromal cells for survival and proliferation, and spontaneously differentiated at low frequency to synthesize hemoglobin. After 9 months in culture, erythroblasts became stroma independent, and they then grew as clonal cell lines. We conclude that PU.1 perturbs the pathway(s) that controls potential for indefinite proliferation and that it can be used to generate permanent erythroblast cell lines.
Mol Cell Biol 1993 Sep
PMID:The Ets-related transcription factor PU.1 immortalizes erythroblasts. 835 8

Infection of cells with adenovirus or transfection of cells with double-stranded RNA (dsRNA) activates transcription of the alpha/beta interferon-stimulated genes (ISGs). Induction of ISG expression by adenovirus appears to be mediated through the same DNA target that is responsive to alpha/beta interferons, the interferon-stimulated response element (ISRE). Transcriptional induction by alpha/beta interferons has been shown previously to be mediated by the activation of a latent cytoplasmic transcription factor, ISGF3, that translocates to the nucleus and binds to the ISRE. However, ISG expression induced by adenovirus or dsRNA appears to be mediated by unique dsRNA-activated factors (DRAFs) that bind to the ISRE. The activation of these preexisting factors by dsRNA does not require new protein synthesis. Two DRAFs, DRAF1 and DRAF2, have been identified in our studies as ISRE-binding complexes in gel mobility shift assays. The ISRE-binding specificity of DRAF1 is similar to that of ISGF3; however, the ISRE-binding specificity of DRAF2 is distinct. Activation of DRAF1 and DRAF2 is independent of interferon action since it occurs in cells that are nonresponsive to interferon and in cells that lack the alpha/beta interferon locus. The activation pathway of DRAF1 and DRAF2 is blocked by the protein kinase inhibitors staurosporine and genistein. This is analogous to the interferon signal transduction pathway and suggests that phosphorylation, possibly tyrosine phosphorylation, is involved in activation of these factors.
Mol Cell Biol 1993 Jun
PMID:Double-stranded RNA activates novel factors that bind to the interferon-stimulated response element. 838 46

Infection with adenovirus type 12 (Ad12) induces four fragile sites in the human genome (H.F. Stich, G.L. van Hoosier, and J.J. Trentin, Exp. Cell Res. 34:400-403, 1964; H. zur Hausen, J. Virol. 1:1174-1185, 1967). The major site, at 17q21-22, contains the U2 gene cluster, which is specifically disrupted by infection in at least a percentage of the cells (D.M. Durnam, J.C. Menninger, S.H. Chandler, P.P. Smith, and J.K. McDougall, Mol. Cell. Biol. 8:1863-1867, 1988). For direct assessment of whether the U2 locus is the target of the Ad12 effect, an artificial locus, constructed in vitro and consisting of tandem arrays of the U2 6-kbp monomer, was transfected into human cells. We report that integration of this artificial locus on the p arm of chromosome 13 creates a new Ad12-inducible fragile site.
Mol Cell Biol 1993 Oct
PMID:Generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial U2 locus in the human genome. 841 8

Inflammation in nasal and airway tissue caused by allergens, microbial infection, and air pollution are likely to be regulated by inflammatory mediators produced by airway epithelial cells. We have therefore investigated the baseline expression of a number of cytokine genes known to be important inducers and modulators of inflammation, in freshly isolated human nasal epithelium. Cells were obtained by superficial scraping of turbinate tissue, and cDNA for polymerase chain reaction (PCR) amplification was reverse-transcribed directly from lysates of 3 x 10(3) to 5 x 10(3) epithelial cells using random hexamers. Constitutive expression of relatively high levels of interleukin-8 (IL-8) mRNA but undetectable levels (< 1 mRNA copy/cell) of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-6, IL-1, or tumor necrosis factor (TNF) mRNA were found after PCR amplification of the cDNA. IL-8 protein, but not IL-6, was identified in the nasal epithelial cells by immunocytochemistry. Infection with respiratory syncytial virus (RSV) or stimulation of nasal epithelium for 4 h with TNF or IL-1 in vitro resulted in a 4- to 10-fold increase in IL-8 mRNA expression but not in the expression of detectable levels of mRNA for the other cytokines. IL-8 was secreted by RSV-, IL-1-, and TNF-stimulated as well as unstimulated nasal epithelial cells after 6 to 20 h of culture. Neither IL-6, GM-CSF, nor TNF activity/immunoreactivity was detectable in the culture supernatants. Thus, it appears that IL-8 is a major cytokine of human nasal epithelium, constitutively expressed and readily secreted upon virus infection or stimulation with IL-1 and TNF.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Interleukin-8 expression in normal nasal epithelium and its modulation by infection with respiratory syncytial virus and cytokines tumor necrosis factor, interleukin-1, and interleukin-6. 841 53

The usefulness of adenovirus type 5 as a vector for homologous recombination was examined in CHO cells by using the adenine phosphoribosyltransferase (aprt) gene. Infection of a hemizygous CHO APRT- cell line containing a 3-bp deletion in exon 5 of the aprt gene with a recombinant adenovirus containing the wild-type gene resulted in restoration of the APRT+ phenotype at a frequency of 10(-5) to 10(-6) per infected cell. A relatively high frequency (approximately 6 to 20%) of the transductants appears to result from a homologous recombination event. The mutation on the chromosomal aprt gene is corrected in the homologous recombinants, and APRT expression is restored to a normal hemizygous level. Neither adenovirus nor exogenous promoter sequences are detected in the homologous recombinants. The remaining transductants result from random integration of the aprt gene with the adenovirus sequence. A number of adenovirus vectors containing different promoter sequences linked to the hamster aprt gene were constructed. A possible role for the promoter region in the homologous recombination event was indicated by the lack of homologous recombination in constructs lacking an active promoter.
Mol Cell Biol 1993 Feb
PMID:Correction of a deletion mutant by gene targeting with an adenovirus vector. 842 11

The acidic carboxy-terminal 89-amino acid fragment of bacteriophage T4 gene 32 protein was expressed in Escherichia coli to high levels from an inducible plasmid construct. Infection of induced cells by wild-type T4 phage results in impaired phage DNA synthesis. The time at which DNA synthesis begins and the diminution in DNA synthesis rates correlate with the amount of carboxy-terminal peptide that accumulates intracellularly prior to infection. Correspondingly, when induced cells are infected with viable phage containing a small deletion near the carboxy-terminus of 32 protein (delta PR201), the inhibition of phage DNA synthesis was much more severe. The mutant 32 protein competes less well against overproduced wild-type acid peptide than does wild-type 32 protein. The purified acid peptide, when used as the attached ligand for affinity chromatography, binds several T4 proteins from phage-infected cells, including 43 protein (T4 DNA polymerase), Dda protein (a DNA helicase), and UvsX protein (a Rec-like recombination protein). Furthermore, at 50- to 100-fold molar excess of acid peptide over intact 32 protein, phage DNA synthesis was specifically inhibited at the initiation step in an in vitro 5-protein DNA replication experiment. We propose that one or more phage replication proteins are titrated as non-productive protein-protein complexes at a site away from the DNA template. This implies that the carboxy-terminal domain of 32 protein is involved in an obligate step of replication machine assembly when the protein is properly attached to ssDNA in the vicinity of a primer-template junction. The assembly defect we observe is strikingly similar to the repression, or "squelching", of the activity of certain eukaryotic transcriptional activators.
J Mol Biol 1993 Jan 20
PMID:Assembly of the bacteriophage T4 replication machine requires the acidic carboxy terminus of gene 32 protein. 842 54

Infection of tobacco by tobacco mosaic virus (TMV) induces coordinate expression of genes encoding acidic and basic beta-1,3-glucanase isoforms. These genes are differentially expressed in response to other treatments. Salicylate treatment induces acidic glucanase mRNA to a higher level than basic glucanase mRNA. Ethylene treatment and wounding strongly induce the basic glucanase genes but have little effect on genes encoding the acidic isoforms. Furthermore, the basic glucanase genes are constitutively expressed in roots and lower leaves of healthy plants, whereas the acidic glucanase genes are not. In order to investigate how these expression patterns are established, we fused promoter regions of an acidic and a basic glucanase gene to the beta-glucuronidase (GUS) reporter gene and examined expression of these constructs in transgenic tobacco plants. A fragment of 1750 bp and two 5'-truncated fragments of 650 bp and 300 bp of the acidic glucanase promoter were tested for induction of GUS gene expression after salicylate treatment and TMV infection. Upstream sequences of 1750 bp and 650 bp were sufficient for induction of the reporter gene by salicylate treatment and TMV infection, but the activity of the 300 bp fragment was strongly reduced. The results suggest that the 1750 bp upstream sequence of the acidic glucanase gene contains multiple regulatory elements. For the basic glucanase promoter it is shown that 1476 bp of upstream sequences were able to drive expression in response to TMV infection and ethylene treatment, but no response was found to incision wounding. Furthermore, high GUS activity was found in lower leaves and roots of healthy transgenic plants, carrying the 1476 bp basic glucanase promoter/GUS construct. When the promoter was truncated up to position -446 all activity was lost, indicating that the region between -1476 and -446 of the basic glucanase promoter is necessary for organ-specific and developmentally regulated expression as well as for induced expression in response to infection and other stress treatments.
Plant Mol Biol 1993 Feb
PMID:Analysis of regulatory elements involved in stress-induced and organ-specific expression of tobacco acidic and basic beta-1,3-glucanase genes. 844 40

A PCR-based screening approach was used to isolate genomic clones from wheat encoding peroxidase isozymes. Three complete genes (pox1, pox2 and pox4) and one truncated gene (pox3) were characterized. The nucleotide sequences predicted mature proteins of 31 kDa, in which all the highly conserved motifs of secreted plant peroxidases were preserved. The coding regions showed 73-83% DNA sequence identity, with the highest level of similarity noted for the tandemly oriented pox2 and pox3. Expression of respective pox genes in various tissues of wheat was assessed by the RT-PCR technique, which showed that all four genes are active. The primary pox1 mRNA was spliced to remove three introns, whereas processing of the other pox transcripts involved only two intervening sequences. Splicing occurred at consensus GU/AG splice sites except for the first introns of pox1, pox2 and pox4 transcripts, where processing took place at unusual GC donor sites. The RNA analysis suggested that the pox1, pox2 and pox4 genes are predominantly expressed in roots. Lower levels of expression were found for pox4 and pox3 in leaves. Infection of wheat by the powdery mildew fungus selectively induced expression of pox2 in leaves.
Plant Mol Biol 1995 Nov
PMID:Molecular cloning and expression analysis of peroxidase genes from wheat. 854 92


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