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

The incidence of sister chromatid exchange (SCE) was investigated in the lymphocytes of 44 pregnant women, 51 users of oral contraceptives (OCs), and 38 controls after culture at 37 C and 40 C. All study subjects were healthy adult females who were not occupationally exposed to mutagens, were nonsmokers, and had no recent viral infection or radiation exposure. At the normal growth temperature of 37 C, the frequency of SCEs/cell was 7.91 + or - 0.30 in pregnant women, 8.53 + or - 0.29 in OC users, and 5.56 + or - 0.21 in controls. When the growth temperature was elevated to 40 C, there was a further increase in the frequency of SCE in all 3 groups: 11.86 + or - 0.44 in pregnant women, 12.76 + or - 0.46 in OC users, and 7.24 + or - 0.26 in controls. Given the significant differences between SCE frequencies of pregnant women and OC users on one hand and controls on the other hand, it can be implied that chromosomes of pregnant women and women using hormonal contraceptives are more susceptible to the damage induced by increases in cell culture temperature. There are also indications that the higher level of hormones present in the blood of pregnant women and OC users may play an important role in increasing the sensitivity of their lymphocytes of genetic damage. The increased induction of SCEs following increased cell culture temperature in pregnant women and OC users may be attributable to the increased efficiency of such a temperature-dependent gyrase-like enzyme on the 1 hand and to the increased mutagenic activity of estrogen or its metabolites on the other hand.
Environ Mol Mutagen 1988
PMID:Sister chromatid exchanges in the lymphocytes of control women, pregnant women, and women taking oral contraceptives: effects of cell culture temperature. 340 74

We investigated the mechanisms by which influenza virus prevents shutoff of protein synthesis by a cellular protein kinase normally activated during infection. Earlier work has shown that influenza virus superinfection of cells previously infected by the adenovirus VAI RNA-negative mutant dl331 resulted in selective translation of influenza virus mRNAs and suppression of the elevated protein kinase levels normally found in cells infected by the mutant alone (M. G. Katze, B. M. Detjen, B. Safer, and R. M. Krug, Mol. Cell. Biol. 6:1741-1750, 1986). We elucidated the mechanisms of this kinase repression and can now report that influenza virus encodes a gene product which functions to directly block the autophosphorylation and activity of the interferon-induced, double-stranded-RNA-activated protein kinase, P68. Suppressed P68 activity was found not only in doubly infected cells but also in cells infected by influenza virus alone. Moreover, the decrease in P68 activity correlated with a decrease in the endogenous levels of phosphorylation of the alpha subunit of the eucaryotic initiation factor eIF-2, the natural substrate of the protein kinase. Suppression of P68 activity occurred as early as 2 h after influenza virus infection and required viral gene expression beyond the level of primary mRNA transcription to take place. We confirmed our in vivo observations with in vitro mixing experiments which showed that the influenza virus inhibitor can act in trans to block P68 activity. Combined repression of P68 function and eIF-2 alpha phosphorylation during influenza virus infection is essential for continued catalytic recycling of eIF-2 and efficient mRNA translation.
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PMID:Influenza virus regulates protein synthesis during infection by repressing autophosphorylation and activity of the cellular 68,000-Mr protein kinase. 341 83

A DNA methyltransferase was isolated from a eucaryotic, Chlorella-like green alga infected with the virus PBCV-1. The enzyme recognized the sequence GATC and methylated deoxyadenosine solely in GATC sequences. Host DNA, which contains GATC sequences, but not PBCV-1 DNA, which contains GmATC sequences, was a good substrate for the enzyme in vitro. The DNA methyltransferase activity was first detected about 1 h after viral infection; PBCV-1 DNA synthesis and host DNA degradation also began at about this time. The appearance of the DNA methyltransferase activity required de novo protein synthesis, and the enzyme was probably virus encoded. Methylation of DNAs with the PBCV-1-induced methyltransferase conferred resistance of the DNAs to a PBCV-1-induced restriction endonuclease enzyme described previously (Y. Xia, D. E. Burbank, L. Uher, D. Rabussay, and J. L. Van Etten, Mol. Cell. Biol. 6:1430-1439). We propose that the PBCV-1-induced methyltransferase protects viral DNA from the PBCV-1-induced restriction endonuclease and is part of a virus-induced restriction and modification system in PBCV-1-infected Chlorella cells.
Mol Cell Biol 1986 May
PMID:DNA methyltransferase induced by PBCV-1 virus infection of a Chlorella-like green alga. 353 3

The concomitant expression of certain oncogenes can transform normal diploid rodent cells into transplantable tumorigenic cells. The mechanism by which these oncogenes collaborate is unclear. Recent findings (M. Oshimura, T. M. Gilmer, and J. C. Barrett, Nature [London] 316:636-639, 1985) raise the possibility that karyotypic changes, including monosomy for chromosome 15, are required to induce tumorigenicity in Syrian hamster embryo cells transfected in vitro with v-Ha-ras and v-myc DNAs. We studied the effect of the oncogenes v-Ha-ras and v-myc, introduced by viral infection, on murine hematopoietic cells. The induction of growth factor independence by the two oncogenes was used as an in vitro correlate of tumorigenicity. After a period of reduced growth rate reminiscent of the growth rate of cells in crisis, the doubly infected cells became growth factor independent. These cells showed a great variability in their karyotypes.
Mol Cell Biol 1986 Oct
PMID:Coinfection with viruses carrying the v-Ha-ras and v-myc oncogenes leads to growth factor independence by an indirect mechanism. 354 May 94

The main nucleocapsid protein (NP) of human epidemic viruses was found to be cleaved via NP56----HP53 mol. wt. reduction in infected cells, while the NP of animal influenza viruses was refractory to analogous intracellular modification. Like animal influenza viruses, the strain A/Baku/799/82(H1N3) isolated from a sick child has been observed to exhibit the intracellular resistance of NP to intracellular proteolysis. The similar NP resistance has been revealed for A/New Jersey/8/76(H1N1) and A/seal/Massachusetts/81 (H7N7) viruses, which are able to induce only a sporadic human influenza viral infection. Thus, the results reveal a correlation between the viral strains epidemicity and intracellular cleavability of their NPs. The influenza viral strains epidemic for humans are characterized by cleavable NP, whereas the strains, which are known to induce the sporadic influenza human infection are found to exhibit the resistance of NP to intracellular proteolysis. It is reasonable to consider the phenomenon of NP56----NP53 proteolytic modification as a sign of viral strain epidemicity for humans.
Mol Gen Mikrobiol Virusol 1987 Feb
PMID:[Intracellular proteolytic cleavage of the influenza virus protein NP as a sign of the epidemicity of virus strains?]. 355 9

Adenosine dialdehyde (2'-O-[(R)-formyl(adenin-9-yl)methyl]-(R)-glyceraldehyde), formed by periodate oxidation of adenosine, is a potent inhibitor of S-adenosylhomocysteine hydrolase (EC 3.3.1.1.) in mouse L929 cells. Consequently, the dialdehyde produces an increase in intracellular levels of S-adenosylhomocysteine and subsequent inhibition of S-adenosylmethionine-dependent macromolecular methylations. In the present study we show that adenosine dialdehyde is also a potent inhibitor of vaccinia virus plaque formation in monolayer cultures of L cells. When added to the culture medium immediately following attachment of the virus, concentrations of the dialdehyde as low as 0.5 microM produce greater than 90% inhibition of plaque formation after 72 hr. The efficacy of the compound is greatest when added within 8 hr of virus attachment and gradually decreases in a time-dependent manner when added after this point. Treatment of L cells with 5 microM adenosine dialdehyde for 60 min prior to virus infection causes a transient, but virtually complete loss of S-adenosylhomocysteine hydrolase activity and subsequent 3-fold increase in the intracellular S-adenosylhomocysteine/S-adenosylmethionine ratio. Continuous exposure of infected cells to the dialdehyde results in prolonged inhibition of S-adenosylhomocysteine hydrolase accompanied by a 10-fold increase in the S-adenosylhomocysteine/S-adenosylmethionine ratio. Associated with these changes in the dialdehyde-treated, infected cells are an inhibition of early virus-specific protein synthesis and a 13% decrease in methylation of the cytoplasmic poly A+-mRNA. The antiviral action of this compound thus appears to be related to a decrease in viral mRNA methylation (e.g., the 5'-terminal cap structure) which results in suppressed translation of viral proteins essential for virus replication.
Mol Pharmacol 1987 May
PMID:Adenosine dialdehyde: a potent inhibitor of vaccinia virus multiplication in mouse L929 cells. 357 93

Small spherical particles produced in the non-permissive phase of hepatitis B virus infection, when the viral genome is integrated into the chromosome of hosts, are rich in the product of the S gene, but poor in the product of the pre-S2 region. For the purpose of adding immunogenicity to spherical particles deficient in the pre-S2 region product, they were conjugated with a synthetic peptide of 19 amino acid residues. The peptide reproduced a hydrophilic area of the pre-S2 region product encoded by viral genomes of subtypes adr, ayw and ayr. The spherical particles supplemented with the pre-S2 peptide raised antibody to the pre-S2 region product in mice, in addition to antibody to the product of the S gene. Antibody to pre-S2 region product, prepared from sera of immunized mice by absorption with the S gene product, bound to spherical particles bearing pre-S2 region product, irrespective of adr, adw, ayw or ayr subtype, and agglutinated hepatitis B virions in immune electron microscopy. Based on the results obtained, the synthetic peptide may prove useful in adding protective efficacy to small spherical particles poor in pre-S2 region product.
Mol Immunol 1987 May
PMID:A synthetic peptide coded for by the pre-S2 region of hepatitis B virus for adding immunogenicity to small spherical particles made of the product of the S gene. 365 94

Selective translation of influenza viral mRNAs occurs after influenza virus superinfection of cells infected with the VAI RNA-negative adenovirus mutant dl331 (M. G. Katze, Y.-T. Chen, and R. M. Krug, Cell 37:483-490, 1984). Cell extracts from these doubly infected cells catalyze the initiation of essentially only influenza viral protein synthesis, reproducing the in vivo situation. This selective translation is correlated with a 5- to 10-fold suppression of the dl331-induced kinase that phosphorylates the alpha subunit of eucaryotic initiation factor eIF-2. This strongly suggests that influenza virus encodes a gene product that, analogous to the adenoviral VAI RNA, prevents the shutdown of overall protein synthesis caused by an eIF-2 alpha kinase turned on by viral infection. Adenoviral mRNA translation was restored to the extract from the doubly infected cells by the addition of the guanine nucleotide exchange factor eIF-2B, which is responsible for the normal recycling of eIF-2 during protein synthesis. This indicates that the residual kinase in the doubly infected cells leads to a limitation in functional (nonsequestered) eIF-2B and hence functional (GTP-containing) eIF-2 and that under these conditions influenza viral mRNAs are selectively translated over adenoviral mRNAs. Addition of double-stranded RNA to the extracts from these cells restored the eIF-2 alpha kinase to a level approaching that seen in extracts from cells infected with dl331 alone and caused the inhibition of influenza viral mRNA translation. This suggests that the putative influenza viral gene product acts against the double-stranded RNA activation of the kinase and indicates that influenza viral mRNA translation is also linked to the level of functional eIF-2. Our results thus indicate that a limitation in functional eIF-2 which causes a nonspecific reduction in the rate of initiation of protein synthesis results in the preferential translation of the better mRNAs (influenza viral mRNAs) at the expense of the poorer mRNAs (adenoviral mRNAs).
Mol Cell Biol 1986 May
PMID:Translational control by influenza virus: suppression of the kinase that phosphorylates the alpha subunit of initiation factor eIF-2 and selective translation of influenza viral mRNAs. 378 77

Coxsackie B viruses (types 1 to 5) are the most frequent reported cause of acute viral myocarditis. To study the pathogenesis of the disease at the cellular level, we simulated an infectious situation by infecting cultured human foetal heart cells with Coxsackie B3 (CB3) virus. Successful replication of this virus could be demonstrated by the presence of virus particles inside cultivated foetal myocytes together with high titres of progeny virus of 10(8) plaque-forming units (PFU) per millilitre culture medium. Within 9 h of infection networks of myocytes lost their ability to contract spontaneously followed by disintegration and replacement by overgrowing fibroblasts which survived the infection. These cells produced CB3 virus continuously over several months, indicating carrier state infection of human myocardial fibroblasts. Human fibroblasts interferon (IFN-beta) was found to act as a potent inhibitor of the replication of this virus. Virus yields could be reduced from 1.2 x 1.8 x 10(5) PFU/ml culture medium when human heart cells were incubated with IFN-beta 20 h prior to challenge with a high input multiplicity of 50 PFU of CB3 virus per cell, demonstrating the major protective role of IFN-beta in CB3 viral infection. It thus appear that IFN-beta might become useful as an antiviral agent in the treatment of Coxsackie myocarditis.
J Mol Cell Cardiol 1985 Feb
PMID:Coxsackie B3 virus can replicate in cultured human foetal heart cells and is inhibited by interferon. 388 51

We have determined the structure of host DNA and viral DNA at the site of integration of Simian virus 40 (SV40) in a line of transformed Balb/c-3T3 cells (SVB400) isolated by single cell cloning after virus infection. Recombinant phage containing integrated viral DNA and flanking host DNA were purified from a genomic library and, in conjunction with restriction endonuclease cleavage analysis of the transformed cell DNA, were used to determine the organization of the integrated viral sequences. There is heterogeneity in the arrangement of the viral sequences resulting from tandem duplications of all or part of the SV40 genome with preservation of the viral-host junctions. The predominant arrangement is the result of tandem duplication of 41% of the SV40 genome from 0.64 to 0.23. Analysis of the structure of integrated viral DNA in SVB400 at different passage numbers and in single cell clones derived from the 20th passage indicated that rearrangements of viral DNA occur after the integration event and continue with passage of the cells. The organization of host sequences before and after the integration of SV40 was determined by restriction endonuclease cleavage analysis of parental 3T3 DNA and SVB400 DNA, and by analysis of recombinant phage isolated from genomic libraries. A deletion of at least 15 X 10(3) bases of host DNA occurred at the site of integration, which indicates that viral integration was not a result of a simple insertion of SV40. Nucleotide sequence analysis of the virus-host junctions showed that retained SV40 sequences were colinear with the viral genome, and that the junctions with SV40 DNA occurred at nucleotide numbers 1377 and 3610. There was no evidence of duplications of viral or host sequences at the junctions, and a comparison of the flanking mouse sequences with the deleted SV40 sequences revealed no significant homology at the point of joining of the two genomes.
J Mol Biol 1984 Aug 15
PMID:Rearrangements of host and viral DNA in mouse cells transformed by simian virus 40. 608 79


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