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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Picornavirus infection induces a profound inhibition of labelling of newly synthesized RNA in some cell lines. EMC virus blocks transcription in L929 cells, particularly at early times during infection. This inhibition is not dependent on virus gene expression, since it occurs with UV-inactivated virus and also in the presence of translation inhibitors. The inhibition can be largely accounted for by the blockade of [3H]nucleoside transport, as suggested by the transport kinetics and incorporation of labelled nucleoside from preloaded cells. The inhibition of transport and incorporation into TCA-precipitable material was observed with pyrimidine (uridine, thymidine and cytosine) and purine nucleosides (adenosine and guanosine), but the blockade by EMC virus was higher with the latter nucleosides. Preloading of cells with any of these nucleosides resulted in a decreased effect on nucleoside incorporation into nucleic acid after virus infection. These results suggest that the inhibition of incorporation of labelled nucleosides into nucleic acid in EMC virus-infected cells can be explained, at least in part, by the decreased pool size of the phosphorylated nucleosides. These effects are not specific for L cells, because they are also observed in other cell lines.
Mol Cell Biochem 1986 Jun
PMID:The inhibition of nucleic acid synthesis in encephalomyocarditis virus-infected L929 cells: effects on nucleoside transport. 242 45

Undifferentiated F9 cells transfected with plasmids encoding adenovirus E1a gene products underwent radical morphological changes. They ceased to express the SSEA-1 stem cell marker antigen and started to express a number of the characteristics of the differentiated state that is induced in F9 cells by treatment with retinoic acid. In particular, they expressed keratin intermediate filaments and acquired the ability to synthesise simian virus 40 tumor antigens after virus infection. The transfected cells expressed the E1a proteins, and this expression was necessary to induce the phenotypic changes, since a coisogenic plasmid encoding only a truncated 70-amino-acid E1a polypeptide and the transfection procedure itself did not detectably after the morphology or marker expression of the F9 stem cells. The phenotypic change was induced by both 13S and 12S cDNA plasmids. We discuss these results in the context of known E1a functions and with reference to the other oncogenes and external factors that can cause F9 cell differentiation.
Mol Cell Biol 1987 May
PMID:The adenovirus Ela gene induces differentiation of F9 teratocarcinoma cells. 243 96

The promoter-specific factor E2F interacts with critical regulatory sequences within the adenovirus E2 promoter. In addition, the level of active factor increases markedly during a virus infection, dependent on E1A function and coincident with the trans activation of E2 transcription. We have purified the E2F factor through a combination of standard biochemical procedures and DNA affinity chromatography. The purified factor was a single polypeptide of 54,000 molecular weight, as determined by UV crosslinking and renaturation of gel-fractionated protein. Addition of affinity-purified factor to an in vitro transcription system resulted in stimulation of transcription from a promoter containing two E2F-binding sites but not promoters lacking binding sites. We thus conclude that E2F is indeed capable of stimulating transcription once it has bound to the promoter.
Mol Cell Biol 1989 Feb
PMID:The adenovirus-inducible factor E2F stimulates transcription after specific DNA binding. 252 14

The adenovirus DNA-binding protein (DBP) is an abundant multifunctional protein located primarily in the nuclei of infected cells. To define sequences involved in nuclear transport of DBP, a series of point and small deletion mutants were constructed via oligonucleotide-directed mutagenesis. Two short stretches of basic amino acids located in the amino-terminal domain (amino acids 42 to 46 and 84 to 89) were identified. Their importance, however, depended on the context in which DBP was expressed. Disruption of either site prevented nuclear localization after transient expression in transfected 293 cells, implying that two nuclear localization signals are necessary for transport of this nuclear protein. In contrast, the mutant DBPs synthesized during viral infection were located either primarily in the nucleus or in the nucleus and cytoplasm, depending on the mutation and the stage of the viral infection. Thus, the nuclear localization defect could be complemented by viral infection, perhaps through the interaction of the mutant polypeptide with a virus-encoded or -induced factor(s).
Mol Cell Biol 1989 Oct
PMID:Nuclear localization of the adenovirus DNA-binding protein: requirement for two signals and complementation during viral infection. 253 Dec 77

In transient expression assays, the adenovirus E1B 19-kilodalton (19K) tumor antigen increases expression from viral promoters and the promoter for the cellular 70-kilodalton heat shock protein (hsp70). To study the mechanism of this effect, we constructed HeLa cell lines that contain stably integrated copies of the 19K gene. Compared with a 19K- control cell line, 19K+ cells produced a significantly higher level of expression from every promoter introduced into the cells by transfection. The 19K protein also increased expression of an RNA polymerase III-transcribed gene but did not affect the level of expression of the endogenous hsp70 gene. The rate of transcription from transfected promoters, as measured by a nuclear run-on assay, was higher in the 19K+ cells than in the 19K- control cells. Furthermore, the level of plasmid DNA remained higher in the 19K+ cell line, suggesting that the 19K protein stabilizes transfected plasmid DNA. The elevated DNA levels seemed to account in full for the increased transcription. The role of the 19K protein in increasing gene expression during viral infection was found to be due to a replication-dependent increase in viral DNA levels. Thus, the 19K protein activates transcription indirectly by producing a higher level of viral or plasmid DNA. The DNA stabilization function of the 19K protein is probably related to the protective role of the 19K protein during viral infection and represents the first example of a viral oncogene product that modulates gene expression by regulating viral and plasmid DNA levels.
Mol Cell Biol 1989 Dec
PMID:The adenovirus E1B 19-kilodalton protein stimulates gene expression by increasing DNA levels. 253 Dec 84

Murine leukemia virus (MuLV) codes for two precursors of the group-specific antigens, Pr65gag and Pr75gag, in vivo. While Pr65gag is the precursor to the virion structural proteins, Pr75gag undergoes glycosylation and is found on the surface of the infected cell as gp85gag, and it is thought to play a role in virus maturation and spread. Pr65gag synthesis starts at an AUG codon within a favourable initiation context (AAUAUGG at positions 618 to 624). The gp85gag start codon is upstream but its precise location is not known. To map the initiation codon of gp85gag, we used deletion and site-directed mutagenesis of the leader sequence of MuLV RNA and in vitro translation of the RNAs. Synthesis of the MuLV gp85gag protein appears to be initiated at a CUG codon located within a favourable context (ACCCUGG at positions 354 to 359 for Moloney-MuLV). The possible function of gp85gag was investigated by expressing Moloney-MuLV and Friend-MuLV proviral DNA and mutants deficient for gp85gag synthesis in mouse and rat cells. The results indicate that the gp85gag protein probably facilitates the spread of virus infection in tissue culture.
J Mol Biol 1989 Jan 20
PMID:CUG initiation codon used for the synthesis of a cell surface antigen coded by the murine leukemia virus. 253 26

Interferons (IFNs) play a key role in the defense against virus infection and the regulation of cell growth and differentiation, in part through changes in specific gene transcription in target cells. We describe several differences between the signal transduction events that result in transcriptional activation of the human gene coding for a guanylate-binding protein (GBP) by alpha interferon (IFN-alpha) and gamma interferon (IFN-gamma). Activation by IFN-alpha was rapid, transient, and cycloheximide resistant. Activation by IFN-gamma was slower, sustained, and delayed by cycloheximide. IFN-gamma led to the formation of a stable intracellular signal which led to continued GBP transcription even if the ligand was withdrawn, whereas IFN-alpha-induced GBP transcription decayed rapidly if IFN-alpha was withdrawn. Perturbations of signaling pathways involving classical second messengers (cyclic AMP, Ca2+, protein kinase C) did not induce GBP transcription. However, various kinase inhibitors blocked the transcriptional response to IFN-gamma but not IFN-alpha, suggesting that a specific and possibly novel kinase is involved in gene activation by IFN-gamma.
Mol Cell Biol 1989 Dec
PMID:Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways. 255 98

Natural or synthetic anti-sense (as) polynucleotides complementary to distinct functional regions of mRNA (asRNA or asDNA) are able to inhibit the expression of any target gene. If certain viral mRNAs important for virus replication are targeted the inhibition of viral infection by asRNA or asDNA takes place. Inhibitory effects of complementary polynucleotides on gene activity in eukaryotic cells is due to the disturbance of translation of corresponding mRNAs as well as to the impairment of their splicing or transportation from the nuclei to cytoplasm. In prokaryotic cells, obviously, only the first factor is operating. The recombinant genes programming anti-viral asRNA can confer the resistance to the infection by other virus to the transformed cells. The resistance to viral infection observed in transgenic animals, expressing asRNA genes, may be considered as a new unnatural form of informational immunity.
Mol Biol (Mosk)
PMID:[Antisense polynucleotides and prospects for their use in fighting viruses]. 267 73

The introduction and stable expression of foreign genes in mammalian hepatocytes have recently been demonstrated by several techniques, including the use of physical approaches such as direct injection of a DNA calcium phosphate precipitate, electroporation of plasmid DNA and the exposure to liposome-erythrocyte ghost complexes as well as the biological approach of infection of primary hepatocyte cultures with retrovirus vectors. Retrovirus-mediated transduction has proven to be highly advantageous in many in vitro gene transfer studies of mammalian cells, and recent results with primary rat liver cultures have begun to define the conditions under which foreign genes can be transduced into hepatocytes in vitro. Fully differentiated hepatocytes are poorly susceptible, if at all, to infection with retroviruses, a phenomenon due at least in part to the fact that cells must undergo replication in order to retroviral integration and gene expression to occur. Hepatocytes are largely resting cells, arrested in G0. Nevertheless, primary cultures of hepatocytes are known to demonstrate a partial de-differentiation in vitro and undergo several rounds of replication. During a narrow period of time early in primary culture correlated roughly with the de-differentiation, adult hepatocytes do become susceptible to efficient infection with retrovirus vectors. In infected cells, gene expression remains relatively stable for the several week duration of the primary culture. It is not known if the restriction of virus infection in hepatocytes is a function of the state of cellular differentiation, of the availability of viral receptors or of other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biol Med 1989 Apr
PMID:Retrovirus vector-mediated gene transfer into hepatocytes. 269 87

The use of alternative 5' splice sites in the simian virus 40 early-transcription unit controls the ratio of large T to small t antigen during viral infection. To study the regulation of these alternative 5' splice sites, we made two mutants which improve the match of the large-T-antigen 5' splice site to the 5' splice site consensus sequence. Whether these mutants were assayed in vitro or in vivo, we found that the efficiency of large-T splicing is increased by improving the match of the large-T-antigen 5' splice site to the consensus. We conclude that the match of a 5' splice site is an important determinant of 5' splice site utilization and that the simian virus 40 large-T-antigen 5' splice site is almost certainly recognized by the U1 small nuclear RNA component of the U1 small nuclear ribonucleoprotein particle.
Mol Cell Biol 1987 Aug
PMID:The natural 5' splice site of simian virus 40 large T antigen can be improved by increasing the base complementarity to U1 RNA. 282 14


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