Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
attempts on producing lymphoid cell line from penaeus monodon by induction with sv40-t and 12s eia oncogenes.in an attempt of in vitro transformation, transfection mediated expression of simian virus-40 (t) antigen (sv40-t) and transduction mediated expression of adenovirus type 12 early region 1a (12s e1a) oncogene were performed in penaeus monodon lymphoid cells. psv3-neo vector encoding sv40-t oncogene and a recombinant baculovirus bacp2-12s e1a-gfp encoding 12s e1a oncogene under the control of hybrid promoters were used. electroporation and lipofection mediated transformation of sv40-t in lymphoid ...201526279116
adenovirus type 12 e1b 55-kilodalton oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin.the tumor suppressor p53-mediated apoptotic response plays an important role in cisplatin resistant in ovarian cancer. the adenovirus (ad) type 12 e1b 55-kda protein binds to p53 and inactivates its transcriptional transactivation function. in this study, we test the hypothesis that ad12 e1b 55-kda oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin. first, we observed the upregulation protein level of p53 target genes in cisplatin-resistant or cisplatin-sensitive ...201525820823
poor growth of human adenovirus-12 compared to adenovirus-2 correlates with a failure to impair pkr activation during the late phase of infection.human adenovirus type 12 (hadv-12) displays a relatively low virulence and slow replication in cultured human cells, which is manifested by premature death of hadv-12-infected cells. whereas hadv-2 induction of ifn-β expression was transient, hadv-12-infected cells maintained high levels of ifn-β expression, protein kinase r (pkr) activation and eif-2α phosphorylation throughout the infectious cycle. the importance of the ifn-inducible pkr kinase in restriction of hadv-12 was supported by the en ...201525462352
coexistence of epstein-barr virus and parvovirus b19 in tonsillar tissue samples: quantitative measurement by real-time pcr.in this study, we aimed to investigate the presence and copy number of six different viruses in tonsillar tissue samples removed surgically because of chronic recurrent tonsillitis or chronic obstructive tonsillar hypertrophy.201424882454
the n terminus of orf virus-encoded protein 002 inhibits acetylation of nf-κb p65 by preventing ser(276) phosphorylation.orf virus-encoded protein 002 (orfv002) inhibits nf-κb signaling pathway by decreasing the acetylation of nf-κb-p65 through interference of nf-κb p65's association with nf-κb p300. however, the precise mechanism of how orfv002 interferes with the nf-κb p65/p300 association is still unknown. due to similarities of the amino acid sequences of orfv002 and the adenovirus type 12 (ad12) e1a protein (e1a-12), we hypothesized that the n-terminal 52 amino acids of orfv002 might play an important role in ...201323536830
tumorigenic adenovirus 12 cells evade nk cell lysis by reducing the expression of nkg2d ligands.activation of natural killer (nk) cells depends on a balance between signals received from activation and inhibitory ligands expressed on the surface of target cells. tumorigenic human adenovirus 12 (ad12) transformed cells express low levels of the nk cell inhibitory ligand mhc i, but do not exhibit increased sensitivity to nk cell lysis compared to their non-tumorigenic counterparts. analysis of the expression of activation ligands that bind to the nkg2d receptor revealed that rae1β and h60 we ...201222445355
inhibition of p53 by adenovirus type 12 e1b-55k deregulates cell cycle control and sensitizes tumor cells to genotoxic agents.adenovirus e1b-55k represses p53-mediated transcription. however, the phenotypic consequence of p53 inhibition by e1b-55k for cell cycle regulation and drug sensitivity in tumor cells has not been examined. in hct116 cells with constitutive e1b-55k expression, the activation of p53 target genes such as the p21, mdm2, and puma genes was attenuated, despite markedly elevated p53 protein levels. hct116 cells with e1b-55k expression displayed a cell cycle profile similar to that of the isogenic hct1 ...201121680522
cytotoxic and cytostatic effects of polyphenols against rat 3y1 fibroblasts transformed by e1a gene of human adenovirus-type-12.toxicity of polyphenols against rat 3y1 fibroblasts and the cells transformed by human adenovirus (ad12-3y1), its eia gene (eia-3y1), or simian virus 40 (sv-3y1) was examined. among the diphenol compounds examined, pyrocatechol (o-diphenol) and hydroquinone (p-diphenol) showed selective toxicity against ad12-3y1 and eia-3y1 cells, while resorcinol (m-diphenol) showed a much weaker non-specific toxicity against these cells. another o-diphenol (dopamine) and triphenols (gallic acid and pyrogallol) ...199321573520
e1a-3y1 cell-specific toxicity of tea polyphenols and their killing mechanism.to screen carcinostatic components in foodstuffs, the toxicity of tea polyphenols was compared between rat 3y1 diploid fibroblasts and a variety of their virally transformed cells. among tea polyphenols tested, epigallocatechin gallate killed 3y1 cells transformed by e1a gene of human adenovirus type 12 (e1a-3y1 cells) at a 100 times lower concentration than the parental 3y1 cells. epigallocatechin gallate also exerted a strong e1a-3y1 cell-specific toxicity, while epicatechin and epicatechin ga ...199521556548
the n terminus of adenovirus type 12 e1a inhibits major histocompatibility complex class i expression by preventing phosphorylation of nf-kappab p65 ser276 through direct binding.the immune-escape strategy employed by human oncogenic adenovirus type 12 (ad12) involves downregulation of major histocompatibility complex class i (mhc-i) transcription by disabling the transactivator nf-kappab (p50/p65). this is accomplished by the ad12 e1a protein (e1a-12), which prevents nf-kappab from becoming phosphorylated by the protein kinase a catalytic subunit (pkac). in this study, we examined the interactions between e1a-12 and nf-kappab. our data show that an e1a-12 mutant retaini ...201020504937
[molecular epidemiology of human adenovirus diarrhea among infants and young children in lanzhou from july 2005 to june 2008].gastroenteritis is a major cause of childhood morbidity and mortality worldwide. adenovirus adv is recognized to be one of the most important pathogens associated with severe dehydrating gastroenteritis. studies reported elsewhere have shown that about 8%-10% of cases with infantile diarrhea are caused by adv and in some areas adv diarrhea even occurred in the form of outbreaks. studies have confirmed that adv infections are also very common in infants and young children in china. this study aim ...200920193145
cryo-electron microscopy structure of an adenovirus-integrin complex indicates conformational changes in both penton base and integrin.a structure of adenovirus type 12 (hadv12) complexed with a soluble form of integrin alphavbeta5 was determined by cryo-electron microscopy (cryoem) image reconstruction. subnanometer resolution (8 a) was achieved for the icosahedral capsid with moderate resolution (27 a) for integrin density above each penton base. modeling with alphavbeta3 and alpha(iib)beta3 crystal structures indicates that a maximum of four integrins fit over the pentameric penton base. the close spacing (approximately 60 a ...200919726496
activation of the interferon-induced stat pathway during an adenovirus type 12 infection.we have previously described a temporal regulation of host cell gene expression during adenovirus type 2 infection (ad2) of primary human fibroblasts. among the eleven percent of genes deregulated by ad2, a large fraction included genes involved in cell cycle, growth control and antiviral defense, consistent with the capacity of ad2 to efficiently master the infected cell and cause an effectively productive infection. adenovirus type 12 (ad12), which belongs to the highly oncogenic subgroup, is ...200919665745
epigenetic mechanisms in human adenovirus type 12 oncogenesis.for the past 30 years, my laboratory has concentrated its work on demonstrating that the epigenetic consequences of foreign dna insertion into established mammalian genomes -de novo dna methylation of the integrate and alterations of methylation patterns across the recipient genome - are essential elements in setting the stage towards oncogenic transformation. we have primarily studied human adenovirus type 12 (ad12) which induces undifferentiated tumors in syrian hamsters (mesocricetus auratus) ...200919429476
identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation.cells transformed by human adenoviruses (ad) exhibit differential capacities to induce tumours in immunocompetent rodents; for example, ad12-transformed rodent cells are oncogenic whereas ad5-transformed cells are not. the e1a gene determines oncogenic phenotype, is a transcriptional regulator and dysregulates host cell gene expression, a key factor in both cellular transformation and oncogenesis. to reveal differences in gene expression between cells transformed with oncogenic and non-oncogenic ...200919200380
induction of neuronal and tumor-related genes by adenovirus type 12 e1a.adenovirus type 12 (ad12) e1a protein (e1a-12) contains a unique 20-amino-acid spacer region between the second and third conserved regions. substitution of a single amino acid in the spacer is able to abrogate ad12 tumorigenesis. to investigate the function of the spacer, microarray analysis was performed on cells transformed by tumorigenic and nontumorigenic ad12s that differ only by one amino acid in the spacer. fewer than 0.8% of approximately 8,000 genes in the microarray exhibited differen ...200918987153
distribution and life history of rat brain tumors induced by human adenovirus type 12 in their early stages of the oncogenesis.newborn rats were intracranially inoculated with human adenovirus type 12 within 24 hours after birth and their brains were sequentially investigated by conventional histological techniques and autoradiography to clarify the early process of tumor growth. at the end of the 2nd week atypical cells having bizarre configuration first appeared singly in the tapetum. from the end of the 3rd week small clusters of slightly atypical subependymal cells ("abnormal clusters") appeared in the subependymal ...198118792756
human car gene expression in nonpermissive hamster cells boosts entry of type 12 adenovirions and nuclear import of viral dna.adenovirus type 12 (ad12) propagation in hamster bhk21 cells is blocked prior to viral dna replication. the amounts of ad12 dna in the nuclei or cytoplasm of hamster cells are about 2 orders of magnitude (2 h postinfection [p.i.]) and 4 to 5 orders of magnitude (48 h p.i.) lower than in permissive human cells. cell line bhk21-hcar is transgenic for and expresses the human coxsackie- and adenovirus receptor (hcar) gene. nuclear uptake of ad12 dna in bhk21-hcar cells is markedly increased compared ...200818256153
tumorigenic adenovirus type 12 e1a inhibits phosphorylation of nf-kappab by pkac, causing loss of dna binding and transactivation.human adenovirus type 12 (ad12) e1a protein (e1a-12) is the key determinant of viral tumorigenesis. e1a-12 mediates major histocompatibility complex class i (mhc-i) shutoff by inhibiting the dna binding of the transcriptional activator nf-kappab (p50/p65) to the class i enhancer. this enables ad12 tumorigenic cells to avoid class i recognition and lysis by cytotoxic t lymphocytes. in this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase a ( ...200817959673
human adenovirus type 12: crossing species barriers to immortalize the viral genome.when viruses cross species barriers, they often change their biological and pathogenetic properties. in the author's laboratory the nonproductive interaction of syrian hamster cells with human adenovirus type 12 (ad12) has been studied. ad12 induces undifferentiated tumors in newborn hamsters (mesocricetus auratus) at high frequency. ad12 inefficiently enters hamster (bhk21) cells, and only small amounts of viral dna reach the nucleus. viral dna replication and late transcription are blocked. in ...200717656784
epigenetic status of an adenovirus type 12 transgenome upon long-term cultivation in hamster cells.the epigenetic status of integrated adenovirus type 12 (ad12) dna in hamster cells cultivated for about 4 decades has been investigated. cell line tr12, a fibroblastic revertant of the ad12-transformed epitheloid hamster cell line t637 with 15 copies of integrated ad12 dna, carries one ad12 dna copy plus a 3.9-kbp fragment from a second copy. the cellular insertion site for the ad12 integrate, identical in both cell lines, is a >5.2-kbp inverted dna repeat. the ad12 transgenome is packaged aroun ...200717344292
fate of adenovirus type 12 genomes in nonpermissive cells.the fate of (3)h-thymidine-labeled adenovirus type 12 deoxyribonucleic acid (dna) was studied in nil-2 cells of syrian hamster origin. it was found that a substantial fraction of (3)h-adenovirus type 12 dna became degraded within 24 hr after infection and was released into the culture fluid. after infection of 5-bromodeoxyuridine (budr)-prelabeled cells with (3)h-adenovirus type 12, viral dna became readily separable from cellular dna by equilibrium centrifugation in cscl. part of the viral radi ...196916789102
antigenic variation among adenovirus type 12 strains. 196516562038
identification of specific cellular genes up-regulated late in adenovirus type 12 infection.the infection of human cells by adenoviruses leads to a gradual reduction in the activity of host cell functions while viral gene expression progresses in a regulated way. we used the dna microarray technique to determine the transcriptional activity profiles of cellular genes upon infection with adenovirus type 12 (ad12). the microarray data were validated by quantitative real-time pcr for genes which showed significant alterations after ad12 infection. at 12 h postinfection, there is a strikin ...200515681441
localization of integrated adenovirus dna in the hamster genome.adenovirus dna integrated into the genomes of adenovirus-transformed hamster cells or of adenovirus type 12 (ad12)-induced hamster tumor cells can be located at many different chromosomal sites. this raises the question as to whether distinct isochores of the hamster cell genome might be more accessible to recombination with adenovirus dna. in ad12- or ad2-transformed hamster cell lines, and in ad12 revertants, the investigated integrated viral dna sequences were assigned to isochore families by ...200415583860
tumorigenesis by adenovirus type 12 in newborn syrian hamsters.ad12 oncogenesis in hamsters has been studied in detail to provide the following new data in this tumor model. cells in the ad12-induced tumors, often thought to be of neuronal origin, actually exhibit mesenchymal and neuronal characteristics and are probably of an undifferentiated derivation. their intraperitoneal spread upon intramuscular injection of ad12 adds another important new aspect. differences in the integration patterns among the tumors suggest clonal origins from individual transfor ...200414674603
sequestration of p53 in the cytoplasm by adenovirus type 12 e1b 55-kilodalton oncoprotein is required for inhibition of p53-mediated apoptosis.the adenovirus e1b 55-kda protein is a potent inhibitor of p53-mediated transactivation and apoptosis. the proposed mechanisms include tethering the e1b repression domain to p53-responsive promoters via direct e1b-p53 interaction. cytoplasmic sequestration of p53 by the 55-kda protein would impose additional inhibition on p53-mediated effects. to investigate further the role of cytoplasmic sequestration of p53 in its inhibition by the e1b 55-kda protein we systematically examined domains in both ...200314645574
intraperitoneal dissemination of ad12-induced undifferentiated neuroectodermal hamster tumors: de novo methylation and transcription patterns of integrated viral and of cellular genes.the intramuscular (i.m.) injection of human adenovirus type 12 (ad12) into newborn syrian hamsters caused widespread dissemination of up to 15 tumors over the entire peritoneal cavity in 70-90% of the animals within 30-50 days. subcutaneous (s.c.) injections led to local tumor formation only. independent of location, tumor histology revealed homer-wright rosette-like structures typical for primitive neuroectodermal tumors (pnet). all tumor cells showed markers indicative of neuroectodermal and m ...200314609629
hemagglutination and hemagglutination-inhibition with adenovirus type 12. 196514254549
tumor immunity in hamsters infected with adenovirus type 12 or simian virus 40. 196414233501
immunofluorescent studies of adenovirus 12 tumors and of cells transformed or infected by adenoviruses.complement-fixing (cf) antibody-positive sera from hamsters bearing adenovirus type 12 (ad. 12)-induced tumors revealed specific immunofluorescent stainable antigens in essentially all ad. 12 hamster tumor cells. the antigens were primarily in the form of cytoplasmic flecks; less frequent staining was seen as nuclear flecks or homogeneous staining of nucleus and cytoplasm of a small proportion of cells. tumor cells did not stain with rabbit antisera to crude ad. 12 virus or a and c antigens. the ...196414212121
characteristics of human adenovirus type 12 induced hamster tumor cells in tissue culture. 196414194601
production of type-specific c antigen in virus-free hamster tumor cells induced by adenovirus type 12. 196414171456
in vitro transformation of hamster kidney cells by human adenovirus type 12. 196414166590
viruses and mammalian chromosomes; chromosome aberrations by human adenovirus type 12. 196414165598
virogenic hamster tumor cells: induction of virus synthesis.virogenic cell cultures of a hamster ependymoma originally produced by simian virus 40 were treated with proflavine, hydrogen peroxide, or mitomycin c. induction of virus synthesis was observed. similar experiments with hamster cells transformed by adenovirus type 12 or polyoma virus gave negative results196414163330
persistent infection of human cells (hela) with adenovirus type 12. 196414159694
adenovirus type 12 infection. clinical and laboratory studies. 196414151175
antibody to adenovirus type 12 among infants. 196414149186
oncogenic effect of human adenovirus type 12, in mice.undifferentiated malignant tumors were induced at the site of injection of human adenovirus type 12 into newborn mice of the c(3)h(f)/ g(8). strain, but not of the dba(f), or a(f) strains. the tumors were grossly and histologically similar to those induced by this virus in hamsters, but appeared in a smaller percentage of injected mice than hamsters.196414075711
acute infectious lymphocytosis presenting as a pertussis-like illness: its association with adenovirus type 12. 196414074503
infection with adenovirus type 12. 196414074502
effect of a possible oncogenic virus (adenovirus type 12) on lactate dehydrogenase in tissue culture. 196414074501
inhibition by 5-iododeoxyuridine of the oncogenic effects of adenovirus type 12 in hamsters.subcutaneous tumors induced in newborn hamsters by type 12 adenovirus were suppressed when 0.5 mg of 5-iodo-2'-deoxyuridine (iudr) was given at the same subcutaneous site as the virus. although one injection of iudr given immediately after the virus was effective, additional injections on subsequent days reduced further the number of hamsters developing tumors. these effects of ludr are especially interesting since replication of infectious adenovirus 12 cannot be demonstrated in the hamsters at ...196314064445
antibody response in rabbits to adenovirus type 12. 196313990410
the abortive infection of syrian hamster cells with human adenovirus type 12.human adenovirus type 12 (ad12) induces undifferentiated tumors in newborn syrian hamsters, and this tumor model has been investigated in detail in our laboratory. one of the characteristics of the ad12-hamster cell system is a strictly abortive infection cycle. in this chapter, we summarize previous and more recent results of studies on the interaction of ad12 with the nonpermissive bhk21 hamster cell line. the block of ad12 replication lies before viral dna replication and late gene transcript ...200312747558
chromatin repression by coup-tfii and hdac dominates activation by nf-kappab in regulating major histocompatibility complex class i transcription in adenovirus tumorigenic cells.in adenovirus type 12 transformed cells, the down-regulation of mhc class i transcription contributes to the tumorigenic phenotype and is solely mediated by ad12 e1a. previous in vitro studies with class i enhancer sequences have indicated that there is an increased binding of repressor coup-tfii and its associated hdac and a decreased binding of activator nf-kappab. in this study, we used chromatin immunoprecipitation (chip) assay in order to determine in vivo whether these proteins regulate cl ...200312620799
integrative recombination between adenovirus type 12 dna and mammalian dna in a cell-free system: joining by short sequence homologies.a cell-free system was developed to investigate the mechanism of how junctions are formed between viral and cellular dnas during adenoviral dna integration into the hamster cell genome. recombination between the segment of adenovirus type 12 (ad12) dna, that comprises sequence coordinates 20885-24053, subsequently termed psti-d fragment and the hamster preinsertion dna sequence p7 was studied in a cell-free system. the p7 dna segment had served as viral dna integration site in the ad12-induced t ...200212457977
differential expression of tapasin and immunoproteasome subunits in adenovirus type 5- versus type 12-transformed cells.adenovirus type 12 (ad12)-transformed baby rat kidney (brk) cells are oncogenic in syngeneic immunocompetent rats in contrast to adenovirus type 5 (ad5)-transformed brk cells, which are not oncogenic in these animals. a significant factor contributing to the difference in oncogenicity may be the low levels of major histocompatibility complex (mhc) class i membrane expression in ad12-transformed brk cells as compared with those in ad5-transformed brk cells, which presumably results in escape from ...200312407112
in adenovirus type 12 tumorigenic cells, major histocompatibility complex class i transcription shutoff is overcome by induction of nf-kappab and relief of coup-tfii repression.the surface levels of major histocompatibility complex class i antigens are diminished on tumorigenic adenovirus type 12 (ad12)-transformed cells, enabling them to escape from immunosurveillant cytotoxic t lymphocytes (ctls). this is due to the down-regulation of the class i transcriptional enhancer, in which there is strong binding of the repressor coup-tfii and lack of binding of the activator nf-kappab. even though nf-kappab (p65/p50) translocates to the nuclei of ad12-transformed cells, it f ...200211884545
the fate of foreign dna in mammalian cells and organisms.we have investigated the consequences of foreign dna insertions into the genomes of mammalian cells in transgenic cell lines, in adenovirus type 12 (ad12)-transformed cells, in ad12-induced tumor cells or in transgenic mice. we have reported previously on the de novo methylation of integrated foreign genomes and on extensive changes in cellular patterns of dna methylation upon foreign dna insertion. these studies have been extended and several independent methods have been applied to document th ...200111761272
foreign dna integration--perturbations of the genome--oncogenesis.we have been interested in the consequences of foreign dna insertion into established mammalian genomes and have initially studied this problem in adenovirus type 12 (ad12)-transformed cells or in ad12-induced hamster tumors. since integrates are frequently methylated de novo, it appears that they might be modified by an ancient defense mechanism against foreign dna. in cells transgenic for the dna of ad12 or for the dna of bacteriophage lambda, changes in cellular methylation and transcription ...200111708490
cellular and early viral factors in the interaction of adenovirus type 12 with hamster cells: the abortive response.the interaction of human adenovirus type 12 (ad12) with syrian hamster cells is remarkable in that there is a block of viral dna replication and late gene transcription. we have screened several cellular factors known to play a role in adenovirus replication for their possible contributions to the interactions of ad12 in the abortive bhk21 hamster cell system. (1) western blot analyses of total protein extracts from ad12- or ad2-infected bhk21 cells do not reveal a significant difference in the ...200111682120
overexpression of the adenovirus type 12 (ad12) ptp or e1a gene facilitates ad12 dna replication in nonpermissive bhk21 hamster cells.in the adenovirus type 12 (ad12) hamster cell system, abortive virus infection is one of the factors associated with the highly efficient oncogenesis in newborn syrian hamsters. we have shown earlier that the replication and efficient late transcription of the ad12 genome are blocked in syrian hamster cells. some of the early ad12 functions are transcribed in these cells, although at a minimal rate. in the present study, we demonstrate that low expression levels of the e1a and precursor to termi ...200111581373
binding of pka-riialpha to the adenovirus e1a12s oncoprotein correlates with its nuclear translocation and an increase in pka-dependent promoter activity.the adenovirus type 12 (ad12) e1a12s oncoprotein utilizes the camp/protein kinase a (pka) signal transduction pathway to activate expression of the viral e2 gene, the products of which are essential for viral replication. a central unsolved question is, however, whether e1a12s interacts directly with pka in the process of promoter activation. we show here that e1a12s binds to the regulatory subunits (r) of pka in vitro and in vivo. interaction depends on the n-terminus and the conserved region 1 ...200111414803
coup-tfii is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of mhc class i transcription.down-regulation of the mhc class i enhancer in tumorigenic ad12 cells is associated with strong binding of coup-tf and negligible binding of activator nf-kappab. by comparison, in nontumorigenic ad5 cells, class i expression is high due to negligible binding of coup-tf and strong binding of nf-kappab. here, we show that coup-tfii, but not coup-tfi, is expressed in ad12-transformed cells. the dramatically stronger dna binding of coup-tfii to the class i enhancer in ad12- compared to ad5-transform ...200111352663
foreign dna integration. genome-wide perturbations of methylation and transcription in the recipient genomes.in hamster cells transgenic for the dna of adenovirus type 12 (ad12) or for the dna of bacteriophage lambda, the patterns of dna methylation in specific cellular genes or dna segments remote from the site of transgene insertion were altered. in the present report, a wide scope of cellular dna segments and genes was analyzed. the technique of methylation-sensitive representational difference analysis (ms-rda) was based on a subtractive hybridization protocol after selecting against dna segments t ...200111278495
cdna micro array identification of a gene differentially expressed in adenovirus type 5- versus type 12-transformed cells.proteins encoded by non-oncogenic adenovirus type 5 and oncogenic adenovirus type 12 differentially affect expression of a number of cellular genes. we have used cdna micro array analysis to identify a cellular gene that is expressed in ad12- but not in ad5-transformed cells. this cellular gene was found to be the gene encoding follistatin-related protein, a tgf-beta inducible gene. consistently, a constitutive factor binding to smad binding elements was found in adenovirus type 12-transformed c ...200011150499
dimeric structure of the coxsackievirus and adenovirus receptor d1 domain at 1.7 a resolution.the coxsackievirus and adenovirus receptor (car) comprises two extracellular immunoglobulin domains, a transmembrane helix and a c-terminal intracellular domain. the amino-terminal immunoglobulin domain (d1) of car is necessary and sufficient for adenovirus binding, whereas the site of coxsackievirus attachment has not yet been localized. the normal cellular role of car is currently unknown, although car was recently proposed to function as a homophilic cell adhesion molecule.200011080637
e1a12s-mediated activation of the adenovirus type 12 e2 promoter depends on the histone acetyltransferase activity of p300/cbp.activation of the transcription unit early region 2 (e2) promoter of the oncogenic adenovirus serotype 12 (ad12), which regulates the expression of proteins essential for viral replication, requires the assembly of a ternary complex consisting of camp response element-binding protein (creb)-1/activating transcription factor (atf)-1, the ad12 12s oncogene product of early region 1a (e1a(12s)), and the co-activator p300/cbp on the e2(ad12) camp response element (e2-cre). here we show that the acti ...200011006273
integrated viral genomes can be lost from adenovirus type 12-induced hamster tumor cells in a clone-specific, multistep process with retention of the oncogenic phenotype.in adenovirus type 12 (ad12)-induced tumor cells, in ad12-transformed cells and in continuously passaged cell lines from these sources, the viral dna is integrated in multiple copies, usually at a single chromosomal location. in different tumors or cell lines, the sites of integration of ad12 dna are all different. rare exceptions exist. in most instances, the integrated viral dna resides very stably in the host cell genomes. however, upon continuous serial passage of such cell lines, the integr ...199910854170
camp-independent activation of the adenovirus type 12 e2 promoter correlates with the recruitment of creb-1/atf-1, e1a(12s), and cbp to the e2-cre.expression of the transcription unit early region 2 (e2) is of crucial importance for adenoviruses because this region encodes proteins essential for viral replication. here, we demonstrate that the e1a(12s) protein of the oncogenic adenovirus serotype 12 activates the e2 promoter in dependence of the n terminus and the conserved region 1. activation is mediated through a camp-response element that is bound by creb-1 and atf-1. moreover, the ad12 e2 promoter is inducible by protein kinase a and ...200010722738
association of histone deacetylase with coup-tf in tumorigenic ad12-transformed cells and its potential role in shut-off of mhc class i transcription.chicken ovalbumin upstream promoter-transcription factor (coup-tf) is an orphan nuclear receptor that represses transcription of many genes. in adenovirus type 12 (ad12) transformed cells, a high level of binding activity of coup-tf to the major histocompatibility complex (mhc) class i enhancer correlates with the down-regulation of class i transcription, which, in turn, contributes to tumorigenesis. the mechanism by which coup-tf represses transcription has yet to be elucidated. here we show th ...200010704340
review: resolution issues in single-particle reconstruction.specific factors that affect the resolution of single-particle reconstructions are discussed. we present reconstructions of six particles (dna-dependent protein kinase catalytic subunit, alphab-crystallin, the ribonucleoprotein vault, hepatitis a virus, adenovirus type 2, and the adenovirus type 12/alpha(v)beta5 integrin complex), which have a variety of symmetries (asymmetric to 60-fold) and a wide range of molecular masses (470 kda to 150 mda). in the case of icosahedral viruses, we have found ...199910600559
e1b 55-kilodalton oncoproteins of adenovirus types 5 and 12 inactivate and relocalize p53, but not p51 or p73, and cooperate with e4orf6 proteins to destabilize p53.the p53 tumor suppressor protein represents a target for viral and cellular oncoproteins, including adenovirus gene products. recently, it was discovered that several proteins with structural and functional homologies to p53 exist in human cells. two of them were termed p51 and p73. we have shown previously that the e1b 55-kda protein (e1b-55 kda) of adenovirus type 5 (ad5) binds and inactivates p53 but not p73. further, p53 is rapidly degraded in the presence of e1b-55 kda and the e4orf6 protei ...200010590106
studies on tumourous and other urogenital patients with respect to antigens of oncogenic adenovirus.the possible connection of viruses with tumours was investigated by serologic examinations. concerning the presence of antibodies against adenoviruses, especially those against the early non-virion antigen of oncogenic adenovirus type 12, approximately 4000 tests were made with sera of 446 urogenital patients with and without tumours and 70 ones with internal diseases. it was found by complement fixation tests that antibodies against non-virion antigens of adenoviruses were present in 53% of uro ...199810379368
two domains within the adenovirus type 12 e1a unique spacer have disparate effects on the interaction of e1a with p105-rb and the transformation of primary mouse cells.transformation of primary rodent cells by functions of the adenovirus type 12 (ad12) early region 1 (e1) is reduced severalfold compared with transformation by e1 of ad2. we analyzed whether the unique spacer region of ad12 e1a that borders the conserved region (cr) 2 and represents an oncogenic determinant of ad12 e1a is involved in this impaired transformation property, putatively by modulating transformation-relevant biological e1a functions. we show that a mutant (e1aspm1) that lacks 12 amin ...199910208919
reduced phosphorylation of p50 is responsible for diminished nf-kappab binding to the major histocompatibility complex class i enhancer in adenovirus type 12-transformed cells.reduced cell surface levels of major histocompatibility complex class i antigens enable adenovirus type 12 (ad12)-transformed cells to escape immunosurveillance by cytotoxic t lymphocytes (ctl), contributing to their tumorigenic potential. in contrast, nontumorigenic ad5-transformed cells harbor significant cell surface levels of class i antigens and are susceptible to ctl lysis. ad12 e1a mediates down-regulation of class i transcription by increasing coup-tf repressor binding and decreasing nf- ...199910022903
coxsackievirus and adenovirus receptor amino-terminal immunoglobulin v-related domain binds adenovirus type 2 and fiber knob from adenovirus type 12.the extracellular region of the coxsackievirus and adenovirus receptor (car) is predicted to consist of two immunoglobulin (ig)-related structural domains. we expressed the isolated car amino-terminal domain (d1) and a car fragment containing both extracellular ig domains (d1/d2) in escherichia coli. both d1 and d1/d2 formed complexes in vitro with the recombinant knob domain of adenovirus type 12 (ad12) fiber, and d1 inhibited adenovirus type 2 (ad2) infection of hela cells. these results indic ...19999882344
insertion of foreign dna into an established mammalian genome can alter the methylation of cellular dna sequences.the insertion of adenovirus type 12 (ad12) dna into the hamster genome and the transformation of these cells by ad12 can lead to marked alterations in the levels of dna methylation in several cellular genes and dna segments. since such alterations in dna methylation patterns are likely to affect the transcription patterns of cellular genes, it is conceivable that these changes have played a role in the generation or the maintenance of the ad12-transformed phenotype. we have now isolated clonal b ...19999882302
studies on tumourous and other urogenital patients with respect to antigens of oncogenic adenovirus.the possible connection of viruses with tumours was investigated by serologic examinations. concerning the presence of antibodies against adenoviruses, especially those against the early non-virion antigens of oncogenic adenovirus type 12, approximately 4000 tests were made with sera of 446 urogenital patients with and without tumours and 70 ones with internal diseases. it was found by complement fixation tests that antibodies against nonvirion antigens of adenoviruses were present in 53% of uro ...19989873934
a tandem array of minimal u1 small nuclear rna genes is sufficient to generate a new adenovirus type 12-inducible chromosome fragile site.infection of human cells with adenovirus serotype 12 (ad12) induces metaphase fragility of four, and apparently only four, chromosomal loci. surprisingly, each of these four loci corresponds to a cluster of genes encoding a small abundant structural rna: the rnu1 and rnu2 loci contain tandemly repeated genes encoding u1 and u2 small nuclear rnas (snrnas), respectively; the psu1 locus is a cluster of degenerate u1 genes; and the rn5s locus contains the tandemly repeated genes encoding 5s rrna. th ...19989557709
adenovirus type 12-induced fragility of the human rnu2 locus requires p53 function.adenovirus type 12 (ad12) infection of human cells induces four chromosomal fragile sites corresponding to the u1 small nuclear rna (snrna) genes (the rnu1 locus), the u2 snrna genes (rnu2), the u1 snrna pseudogenes (psu1), and the 5s rrna genes (rn5s). ad12-induced fragility of the rnu2 locus requires u2 snrna transcriptional regulatory elements and viral early functions but not viral replication or integration, or chromosomal sequences flanking the rnu2 locus. we now show that ad12 cannot indu ...19989557707
identification of specific amino acid residues of adenovirus 12 e1a involved in transformation and p300 binding.the early region 1a (e1a) gene of highly oncogenic adenovirus type 12 (ad12) was analyzed for transforming activity and protein binding using specific mutations. the ad12 e1a proteins were found to bind p300 protein mainly within the cr1 region, although mutations that affect both p300 binding and transformation were identified in both the cr1 and the n-terminal region. the most critical mutation dlf89 located in the cr1 region was further dissected by point mutations and the results identified ...19979421880
e1a 12s and 13s of the transformation-defective adenovirus type 12 strain cs-1 inactivate proteins of the rb family, permitting transactivation of the e2f-dependent promoter.the transformation-defective vero cell host range mutant cs-1 of the highly oncogenic adenovirus type 12 (ad12) (ad12-cs-1) has a 69-bp deletion in the early region 1a (e1a) gene that removes the carboxy-terminal half of conserved region 2 and the amino-terminal half of the ad12-specific so-called spacer that seems to play a pivotal role in the oncogenicity of the virus. despite its deficiency in immortalizing and transforming primary rodent cells, we found that the e1a 13s protein of ad12-cs-1 ...19979371617
adenovirus type 12 dna firmly associates with mammalian chromosomes early after virus infection or after dna transfer by the addition of dna to the cell culture medium.human adenovirus type 12 (ad12) infects human cells productively and leads to viral replication, whereas infection of hamster cells remains abortive, with total blocks in viral dna replication and late viral gene transcription. the intranuclear fate of ad12 dna in productively infected human cells and in abortively infected hamster cells was monitored by using the fluorescent in situ hybridization (fish) technique. human hela cells, primary human umbilical cord fibroblasts, hamster bhk21 cells, ...19979311883
adenovirus type 12 early region 1b 54k protein significantly extends the life span of normal mammalian cells in culture.the life span of normal human cells in culture is extended by two to four total life spans following retrovirus-mediated transfer of the adenovirus type 12 e1b 54,000-molecular-weight protein (54k protein). this extension of the in vitro growth potential was accomplished without any of the obvious changes in morphology or growth properties that are usually associated with viral transformation. these 54k+ cells escape the normal senescence checkpoint (m1) and show a very extended secondary growth ...19979261385
clonal origin of adenovirus type 12-induced hamster tumors: nonspecific chromosomal integration sites of viral dna.the mechanism of tumor induction by human adenovirus type 12 (ad12) in newborn syrian hamsters (mesocricetus auratus) has been investigated further. tumors were produced in newborn hamsters by the s.c. injection of cscl-purified ad12. in 60-70% of the surviving animals, tumors have been observed between 33 and 47 days after injection. in 60 independently elicited tumors, the patterns of ad12 dna integration have been studied by restriction enzyme analyses and southern blot hybridization using ad ...19979230215
delayed cytocidal effect of lignin derivatives on virally transformed rat fibroblasts.when rat fibroblasts (ad12-3y1-z19) transformed with adenovirus type 12 were cultured with lignin derivative (acetyl or sulfonyl), the cells grew for 2 to 3 days at the same rate as the control cells cultured without lignin derivative, then rapidly died. this cytocidal effect was independent of the cell population density. the lag time was longer than the doubling time (-24 h) of ad12-3y1-z19 cells. other polyanions such as dextran sulfate and glycosaminoglycans did not show significant inhibito ...19979101070
investigation of oesophageal adenocarcinoma for viral genomic sequences.overexpression of the tumour suppressor gene product p53 is common in oesophageal adenocarcinoma. this may be due to gene mutation, but overexpression can also result from complexing between viral proteins and p53; a number of viruses are causally linked with malignancy. this study therefore investigated the prevalence in oesophageal adenocarcinoma of viruses whose gene products are capable of interacting with p53. seventeen tumours and 17 normal oesophagi were screened for specific dna sequence ...19979066743
the e1a n terminus (aa 1-29) of the highly oncogenic adenovirus type 12 harbours a trans-activation function not detectable in the non-oncogenic serotype 2.early region 1a (e1a) of adenoviruses (ad) codes for potent activator and repressor molecules which are involved in the regulation of viral and cellular gene expression. gene regulatory functions of e1a proteins are mainly located in their conserved regions (cr) 1 to 3. in addition to the crs, specific amino acids (aa) of the n-terminal end play an important role in some gene regulatory functions. we describe here the identification and characterization of a novel trans-activation domain which i ...19979018064
the mhc-encoded tap1/lmp2 bidirectional promoter is down-regulated in highly oncogenic adenovirus type 12 transformed cells.cells transformed by human adenovirus 12 (ad12) exhibit extremely low surface levels of mhc class i molecules and contain reduced levels of class i heavy chain mrnas. we report that levels of mhc-encoded tap1 and lmp2 mrnas are also down-regulated in ad12-transformed rat cells, and that transcription of rat tap1 and lmp2 transcripts is directed from a 564 bp intergenic region which is significantly less active in ad12-transformed cells compared to those transformed with ad5. our results suggest ...19979001385
early stage of human adenovirus type 12-inoculated retinal tissue of f344 newborn rat.to elucidate the pathogenesis of adenovirus type 12 (ad12)-induced rat retinal tumor, an experimental animal model of human retinoblastoma (rb), dna analysis, in situ hybridization and immunohistochemistry were performed. the adenovirus oncogene e1a was detected in the host genome by southern blot hybridization. examined retinal tissues did not show any histological changes, but the number of retinal cells immunoreactive with an antibody to proliferating cell nuclear antigen (pcna) increased wit ...19968893223
insufficient levels of nfiii and its low affinity for the origin of adenovirus type 12 (ad12) dna replication contribute to the abortive infection of bhk21 hamster cells by ad12.human adenovirus type 12 (ad12) induces undifferentiated sarcomas in neonate syrian hamsters and hence presents a suitable model for studies of the molecular mechanism of viral oncogenesis. since we submit that an understanding of the early steps in the interaction between ad12 and hamster cells might shed light on the initiation of malignant transformation, the abortive infection of bhk21 hamster cells with ad12 has been investigated in detail. ad12 replication in these cells is blocked in earl ...19968892924
lack of effect of mouse adenovirus type 1 infection on cell surface expression of major histocompatibility complex class i antigens.it has been proposed that adenoviruses establish and maintain persistent infections by reducing the class i major histocompatibility complex-associated presentation of viral antigens to cytotoxic t lymphocytes, leading to ineffective cell-mediated immunity and impaired clearance of infected cells (w.s.m. wold and l. r. gooding, virology 184:1-8, 1991). early region 3 of human adenovirus types 2 and 5 encodes a 19-kda glycoprotein that associates with the class i major histocompatibility complex ...19968764061
the structure of adenovirus type 12 dna integration sites in the hamster cell genome.foreign dna can integrate into the genomes of mammalian cells, and this process plays major roles in viral oncogenesis and in the generation of transgenic organisms and will be important in evolving regimens for human somatic gene therapy. in the present study, the insertion sites of adenovirus type 12 (ad12) dna genomes have been analyzed in detail in the ad12-transformed hamster cell line t637, its revertants, which have lost most of the >20 ad12 genome equivalents integrated chromosomally in ...19968648714
repression of c-jun-induced mouse major histocompatibility class i promoter (h-2kb) activity by the adenovirus type 12-unique 52r e1a protein.down-regulation of major histocompatibility (mhc) class i gene expression by protein products of the early region 1a (e1a), which might allow transformed cells to escape the host immune system, is discussed as one cause for the oncogenicity of adenovirus (ad) subtype 12-transformed cells. the mhc class i promoter is activated through several cellular-transcription factors among them ap-1, whose target sequences are located in the enhancers a and b, and nf kappa b. in this report we present evide ...19968622892
selective loss of unmethylated segments of integrated ad12 genomes in revertants of the adenovirus type 12-transformed cell line t637.we have studied the stability of integrated adenovirus type 12 (ad12) dna sequences and the relation of foreign dna persistence to the state of methylation of this dna. in the ad12-transformed hamster cell line t637, multiple copies of ad12 dna are chromosomally integrated. some of these integrated viral genomes are rearranged in that internal parts of the viral dna have become juxtaposed to its left terminus. fluorescent in situ hybridization analyses demonstrate that the ad12 dna in cell line ...19958578863
chromosomal distribution of the hamster intracisternal a-particle (iap) retrotransposons.the retrotransposon-like elements of the intracisternal a-particle (iap) sequences occur in about 900 copies per haploid hamster cell genome. by applying the fluorescent in situ hybridization (fish) technique and four different, cloned segments of the iap element as hybridization probes, these elements were found to be distributed in specific patterns over many of the 44 hamster chromosomes. the hybridization patterns were very similar regardless of whether all four probes or only the iapi probe ...19968575245
induction of differentiation-regulated transcription factor oct-6 specifically accompanies major histocompatibility complex class i down-regulation by e1a of oncogenic adenovirus type 12.the e1a genes from adenovirus (ad) types 5 and 12 share the capacity to cooperate with a second oncogene to transform primary rodent cells in vitro. however, only ad12-transformed cells are oncogenic in immunocompetent rodents, an event that requires conserved region 3 (cr3) of e1a to be intact. ad12-induced tumorigenicity correlates with the e1a-cr3-dependent down-modulation of mhc class i transcription, contributing to escape from ctl-mediated immune surveillance. expression of mhc class i ant ...19958547226
evidence for the involvement of a nuclear nf-kappa b inhibitor in global down-regulation of the major histocompatibility complex class i enhancer in adenovirus type 12-transformed cells.diminished expression of major histocompatibility complex class i antigens on the surface of adenovirus type 12 (ad12)-transformed cells contributes to their high tumorigenic potential by enabling them to escape immune recognition by cytotoxic t lymphocytes. this low class i antigen expression is due to a block in class i transcription, which is mediated by ad12 e1a. genetic analysis has shown that the class i enhancer is the target for transcriptional down-regulation. in this study, we show tha ...19968524321
a unique mitigator sequence determines the species specificity of the major late promoter in adenovirus type 12 dna.human adenovirus type 12 (ad12) cannot replicate in hamster cells, whereas human cells are permissive for ad12. ad12 dna replication and late-gene and virus-associated rna expression are blocked in hamster cells. early ad12 genes are transcribed, and the viral dna can be integrated into the host genome. ad12 dna replication and late-gene transcription can be complemented in hamster cells by e1 functions of ad2 or ad5, for which hamster cells are fully permissive (for a review, see w. doerfler, a ...19938419643
generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial u2 locus in the human genome.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 whet ...19938413208
transformation by viral oncogenes increased sensitivity to heat in rat 3y1 fibroblasts.sensitivity to the lethal effect of hyperthermia was compared using the rat 3y1 fibroblastic cell line and its seven sublines transformed by various agents in vitro. the cell lines examined were those transformed by simian virus 40 (sv3y1), mouse polyoma virus (py3y1), adenovirus type 12 (ad3y1), the e1a region of adenovirus type 12 (e1a3y1), rous sarcoma virus (sr3y1), v-harvey ras oncogene (hr3y1) and n-methyl-n-nitro-n-nitrosoguanidine (ng3y1). we also examined the intracellular amount and di ...19938394681
recognition of a palindromic dna sequence by esf-1, a factor stimulating transcription of the adenovirus type 12 e1a gene.we previously identified a factor, designated e1a-stimulating factor 1 (esf-1), that stimulates transcription of the adenovirus type 12 e1a gene in vitro by binding to a region next to a tata box. we report here on the partial characterization of the mode of esf-1 action. point mutations within the nucleotide sequence 5'-tcagctga-3' abolished the binding of esf-1. stimulation of transcription of the adenovirus type 12 e1a gene in vitro was lost when a 7 base pair insertion was introduced between ...19938369759
fractionated nuclear extracts from hamster cells catalyze cell-free recombination at selective sequences between adenovirus dna and a hamster preinsertion site.we have explored the mechanism of adenovirus type 12 (ad12) dna integration because of its importance for viral oncogenesis and as an example of insertional recombination. we have used a fractionated cell-free system from nuclear extracts of hamster cells and have partly purified nuclear proteins that could catalyze in vitro recombination. as recombination partners, the 20,880- to 24,049-nucleotide pst i d fragment of ad12 dna and the hamster preinsertion sequence p7 from the ad12-induced tumor ...19938346256
antipeptide antibodies to adenovirus e1b protein indicate enhanced risk of celiac disease and dermatitis herpetiformis.the relationship between adenovirus type 12 (ad12), celiac disease (cd) and dermatitis herpetiformis (dh) was evaluated by enzyme-linked immunosorbent assay (elisa). diagnostic phase serum samples from 44 children with cd, 16 children with dh and 60 matched controls were studied for serum antibodies to synthetic peptides derived from an early e1b protein of ad12 and a gliadin. both the patient groups had significantly (p < 0.001) higher igg antibody levels to the ad12 e1b peptide than the contro ...19938324388
non-homologous recombination between adenovirus and acnpv dna fragments in cell-free extracts from insect spodoptera frugiperda nuclei.in previous work, we have developed a cell-free system from nuclear extracts of hamster cells to study the mechanism of integrative recombination between adenovirus type 12 (ad12) dna and hamster cell dna (jessberger et al., 1989; tatzelt et al., 1992). we have also demonstrated that in insect cells the left terminal fragment of ad2 dna can insert by non-homologous recombination into the 32.6 to 34.5 map unit (ecori-o) fragment and into other segments of autographa californica nuclear polyhedros ...19938317144
adenovirus type 12 early region 1a expresses a 52r protein repressing the trans-activating activity of transcription factor c-jun/ap-1.oncoproteins of the early transcription unit 1a (e1a) of adenoviruses (ad) are known to modulate the expression of all viral and of a variety of cellular genes. in this communication we present data demonstrating for the first time an activity associated with a protein (the 52r protein) expressed exclusively from e1a of the highly oncogenic subtype ad12. the 52r protein, which does not contain any of the conserved regions (cr1-cr3) necessary for the trans-regulatory functions of the larger e1a p ...19948291251
tumorigenicity of adenovirus-transformed rodent cells is influenced by at least two regions of adenovirus type 12 early region 1a.chimeric adenovirus type 5 (ad5)/ad12 early region 1a (e1a) genes were used to transform primary baby rat kidney cells in cooperation with ad12 e1b, and the resulting cell lines were assayed for tumorigenicity in syngeneic rats. it was found that lines were nontumorigenic when transformed by hybrid e1a genes consisting of the amino-terminal 80 amino acids from ad12 including conserved region 1 (cr1), with the remaining portion from ad5. in contrast, cell lines transformed by hybrids containing a ...19948289391
Displaying items 1 - 100 of 619