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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
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
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
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
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
[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
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
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
altered phosphorylation and oligomerization of p53 in adenovirus type 12-transformed cells.loss of function of the tumor-suppressor protein p53 is, in general, either caused by mutation, inducing a conformational change, or by binding to inactivating cellular (e.g. mdm2) or viral (e.g. sv40 large t) proteins. in adenovirus type 12 (ad12)-transformed cells, p53 is stabilized without detectable binding to the ad12 e1b/54 kda protein and still present in a wild-type conformation but contains a mutant-like activity in cellular transformation. in this study we examined whether the changed ...19957624131
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
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
on the insertion of foreign dna into mammalian genomes: mechanism and consequences.we have studied the integration of adenovirus type 12 (ad12) dna in transformed and hamster tumor cells over many years. upon infection of hamster cells with ad12, viral dna has been found in association with hamster chromosomes, possibly in part integrated into the host genome. ad12 dna integration is not sequence specific. transcriptionally active sites of the host genome show a preponderance for foreign dna insertion. we are pursuing the mechanism of ad12 dna integrative recombination in a ce ...19957607499
adenovirus type 12-induced fragility of the human rnu2 locus requires u2 small nuclear rna transcriptional regulatory elements.infection of human cells with oncogenic adenovirus type 12 (ad12) induces four specific chromosome fragile sites. remarkably, three of these sites appear to colocalize with tandem arrays of genes encoding small, abundant, ubiquitously expressed structural rnas--the rnu1 locus encoding u1 small nuclear rna (snrna), the rnu2 locus encoding u2 snrna, and the rn5s locus encoding 5s rrna. recently, an artificial tandem array of the natural 5.8-kb u2 repeat unit has been shown to generate a new ad12-i ...19957565777
the complete nucleotide sequence of the dna of human adenovirus type 12. 19957555068
downregulation of mhc class i expression due to interference with p105-nf kappa b1 processing by ad12e1a.we have previously demonstrated that expression of major histocompatibility complex (mhc) class i genes is repressed in baby rat kidney cells transformed by early region 1 of oncogenic adenovirus type 12 (ad12e1). reduced expression of mhc class i antigens contributes to the escape of ad12-transformed cells from t-cell-mediated immune surveillance and to tumour induction. in this study, we show that repression of mhc class i expression by ad12e1a is mediated via the h2tf1 element of the mhc clas ...19957729425
the initiation of de novo methylation of foreign dna integrated into a mammalian genome is not exclusively targeted by nucleotide sequence.the de novo methylation of foreign dna integrated into the mammalian genome is a fundamental process whose mechanism has not yet been elucidated. we have studied de novo methylation in adenovirus type 12 (ad12) genomes inserted into the genomes of ad12-induced hamster tumor cells. de novo methylation of ad12 dna, which is not methylated in the virion, is initiated in two paracentrally located regions and spreads from there across the integrated ad12 genomes. (i) after extensive cultivation of cl ...19957815498
activation of the nuclear oncogenes n-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 e1 region gene.the adenovirus (ad) e1 region genes, e1a and e1b, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as n-myc and c-jun, in transfected cell lines. however, there is still less information available on the in vivo mechanism(s) by which the e1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. to investigate such in ...19957865136
heritable formation of neuroectodermal tumor in transgenic mice carrying the combined e1 region gene of adenovirus type 12 with the deregulated human renin promoter.adenovirus early 1 (e1) region gene products, including e1a and e1b, are required for transcriptional regulation of viral and cellular promoters in infected and transfected culture cells and for transformation of primary rodent cells. here, we established a line of transgenic mice carrying the e1 region gene of human adenovirus type 12 under the control of the human renin promoter, in which a neuroectodermal tumor derived from retroperitoneal, olfactory, and/or pelvic regions was heritably devel ...19957542254
regulation of viral and cellular gene expression by e1a proteins encoded by the oncogenic adenovirus type 12. 19957555085
the transcriptionally competent u2 gene is necessary and sufficient for adenovirus type 12 induction of the fragile site at 17q21-22.adenovirus type 12 induces four fragile sites upon infection of human cells. the u2 locus, consisting of up to 20 tandem repeats of a 5.8-kbp monomer, maps at the most sensitive of these sites at 17q21-22. we have previously shown that an artificial u2 locus integrated into the human genome generates a new virus-induced fragile site. to determine which elements within the u2 monomer are responsible for fragility, we constructed loci consisting of tandem repeats of subfragments of the u2 monomer. ...19957565778
distinct modulation of p53 activity in transcription and cell-cycle regulation by the large (54 kda) and small (21 kda) adenovirus e1b proteins.p53 can both stimulate transcription via the p53-consensus sequence as well as inhibit gene expression via caat-tata-sequences. certain viral and cellular proteins can abrogate the p53-dependent stimulation of transcription by physical association. in addition, it has been shown that the large e1b protein of adenovirus type 12 (ad12), e1b/54 kda, can block the transcription activation potential of p53, without binding to p53. here we show that this e1b/54-kda protein also can prevent the repress ...19957571424
repression of the c-jun trans-activation function by the adenovirus type 12 e1a 52r protein correlates with the inhibition of phosphorylation of the c-jun activation domain.the early region 1a 52r polypeptide, a protein expressed exclusively by the in vivo oncogenic adenovirus subtype 12, represses the trans-activating function of the cellular transcription factor complex ap-1 consisting of c-jun-c-jun homodimers. in this report we demonstrate that the repression in vivo correlates with a direct physical interaction of the adenovirus protein with c-jun in vitro. interestingly, the 52r protein binds to the bzip domain of c-jun essential for dimerization and dna bind ...19957738014
chromosomal insertion of foreign (adenovirus type 12, plasmid, or bacteriophage lambda) dna is associated with enhanced methylation of cellular dna segments.insertion of foreign dna into an established mammalian genome can extensively alter the patterns of cellular dna methylation. adenovirus type 12 (ad12)-transformed hamster cells, ad12-induced hamster tumor cells, or hamster cells carrying integrated dna of bacteriophage lambda were used as model systems. dna methylation levels were examined by cleaving cellular dna with hpa ii, msp i, or hha i, followed by southern blot hybridization with 32p-labeled, randomly selected cellular dna probes. for s ...19957777540
cooperatively between an upstream tata-like sequence and a caa repeated element mediates e1a-dependent negative repression of the h-2kb class i gene.in primary rodent cells transformed by the e1a region of the highly oncogenic adenovirus type 12, repression of transcription mediated by the far upstream tata-like element was observed only in conjunction with either possible juxtaposition of a caa repeated element in the presence of e1a and was dependent upon the relative arrangement of both the tata-like and caa repeated motifs in both homologous and heterologous promoter constructs. a gel shift competition study demonstrated that the tata-bi ...19957836466
altered host range phenotype of the transformation-defective ad12 mutant cs-1 is due to deletions in the e1 region.although it grows well in bulk infection, human adenovirus type 12 (ad12) does not plaque efficiently in vero cells of simian origin. after long-term passage of the virus or after transfection of ad12 dna into these cells, however, transformation-defective, host-range mutants giving high plaque yields in vero cells were isolated. the original mutants have deletions in both e1a and e1b as well as additions of viral sequences at the right terminus of the genome. we have constructed a recombinant v ...19947928288
antibody response to adenovirus e1b-derived synthetic peptides and serum levels of p53 in patients with gastrointestinal and other malignant lymphomas.serum levels of p53 and antipeptide antibody levels to adenovirus type 12 (ad12) e1b protein were measured in a case-control study of 62 newly diagnosed patients with malignant lymphoma. while patients with gastrointestinal lymphoma did not differ from their matched controls, p53 positive lymphoma patients had significantly (p < 0.04) increased antipeptide igg antibody levels to the ad12 e1b. concomitant detection of serum p53 and antipeptide antibodies to ad12 e1b was associated with an increas ...19947964649
vitronectin receptor antibodies inhibit infection of hela and a549 cells by adenovirus type 12 but not by adenovirus type 2.the penton base gene from adenovirus type 12 (ad12) was sequenced and encodes a 497-residue polypeptide, 74 residues shorter than the penton base from ad2. the ad2 and ad12 proteins are highly conserved at the amino- and carboxy-terminal ends but diverge radically in the central region, where 63 residues are missing from the ad12 sequence. conserved within this variable region is the sequence arg-gly-asp (rgd), which, in the ad2 penton base, binds to integrins in the target cell membrane, enhanc ...19947520097
a multimegabase cluster of snrna and trna genes on chromosome 1p36 harbours an adenovirus/sv40 hybrid virus integration site.adenovirus type 12 (ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42-43 and 17q21 after infection of human embryonic kidney cells. three of these bands harbour small nuclear rna genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. a non-lytic ad5/sv40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. chromosomal band 1p36 encodes genes for small nuclear rna u1 (rnu-1) and fo ...19947881409
neuroectodermal tumors expressing c-, l-, and n-myc in transgenic mice that carry the e1a/e1b gene of human adenovirus type 12.adenovirus early 1 (e1) region gene products, including e1a and e1b, are required for transformation of primary cultured rodent cells. in order to investigate in vivo action of the e1 region, we established a line of transgenic mice carrying the oncogenic e1a and e1b genes of human adenovirus type 12 under control of the human angiotensinogen promoter. histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying de ...19947983069
transcription stimulation of the adenovirus type 12 e1a gene in vitro by the 266-amino-acid e1a protein.we previously showed that the 13s but not the 12s mrna product of the e1a gene of the highly oncogenic type 12 adenovirus (ad12) stimulates the expression of its own gene. in this study, the mechanism for the autoregulation of the ad12 e1a gene was investigated in vitro. the 266-amino-acid e1a protein of ad12 was synthesized in yeast cells and purified as a 57-kda polypeptide. the purified ad12 e1a protein stimulated transcription from the proximal promoter of its own gene but had almost no effe ...19948035506
negative regulation by the r2 element of the mhc class i enhancer in adenovirus-12 transformed cells correlates with high levels of coup-tf binding.the transcriptional down-regulation of the major histocompatibility complex (mhc) class i antigens in adenovirus type 12 (ad12) transformed cells gives them the potential to escape immunosurveillance and to form tumors. the enhancer of the class i promoter is the target of transcriptional repression which is mediated by the e1a gene of ad12. the r2 region within the class i enhancer acts as a negative element in ad12-transformed cells and exhibits a stronger binding activity than is observed in ...19948036004
e1a oncogene of adenovirus-12 mediates trans-repression of mhc class i transcription in ad5/ad12 somatic hybrid transformed cells.reduction of the major histocompatibility complex (mhc) class i antigens on the surface of adenovirus type 12 (ad12) transformed cells is thought to contribute to their tumorigenic potential. the e1a gene of ad12 mediates this effect by repressing the mhc class i transcriptional enhancer. by contrast, ad5-transformed cells are not blocked in class i gene expression and are nontumorigenic. because e1a proteins modulate transcription by interacting with several different cellular factors, we inqui ...19948053163
tissue-specific trans-activation of renin gene by targeted expression of adenovirus e1a in transgenic mice.we generated two transgenic mice carrying the adenovirus type 12 e1 region genes under control of the human renin promoter, in which the e1a and e1b genes were expressed predominantly in the kidney. interestingly, renal transcription of the gene for mouse renin was shown to be elevated at 28 and 40 folds as compared in those of control animals, but histone mrna levels were unchanged. although the transfected mouse renin promoter was promiscuously trans-activated by e1a in hela cells where the en ...19948123010
late transcripts of adenovirus type 12 dna are not translated in hamster cells expressing the e1 region of adenovirus type 5.hamster cells are completely nonpermissive for the replication of human adenovirus type 12 (ad12), whereas types 2 and 5 can replicate in hamster cells. the ad5-transformed hamster cell line bhk297-c131, which carries the left terminal 18.7% of the ad5 genome and expresses at least the viral e1a region, can somehow complement ad12 dna replication and the transcription of the late ad12 genes. since the interaction of ad12 with hamster cells must constitute a significant factor in the induction of ...19948057430
selective sites of adenovirus (foreign) dna integration into the hamster genome: changes in integration patterns.we investigated whether, upon the integration of multiple copies of adenovirus type 12 (ad12) dna into an established mammalian (hamster) genome, the pattern of foreign dna insertion would remain stable or change with consecutive passages of cells in culture. by the injection of purified ad12 into newborn hamsters, tumors were induced, cells from these tumors were cultivated, and five independent cell lines, ht5, h201/2, h201/3, h271, and h281, were established. these cell lines carried differen ...19948254728
nucleotide sequence of human adenovirus type 12 dna: comparative functional analysis.a fresh inoculum of human adenovirus type 12 (ad12) was obtained from the american type culture collection and passaged once on human embryonic kidney cells, and ad12 dna was prepared from the first-passage yield to avoid higher passages which might have generated host-virus dna recombinants. the 18 psti fragments of ad12 dna were cloned into the pbluescript ks vector, and the entire nucleotide sequence of both strands from all 18 fragments was determined by using successive oligodeoxyribonucleo ...19948254750
constructing chimeric type 12/type 5 adenovirus e1a genes and using them to identify an oncogenic determinant of adenovirus type 12.the e1a gene of highly oncogenic type 12 adenovirus (ad12) possesses a segment unique to this serotype and comprising 60 base pairs contiguous with and separating conserved regions 2 and 3 in the gene. a similar but slightly longer segment is also present in the e1a gene of highly oncogenic simian adenovirus type 7 (d. kimelman, j. s. miller, d. porter, and b. e. roberts, j. virol. 53:399-409, 1985). this segment is missing entirely from the e1a gene of type 5 adenovirus, which is nononcogenic. ...19948289390
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
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
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
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