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expression of human papillomavirus type 6b e2 gene product with dna-binding activity in insect (bombyx mori) cells using a baculovirus expression vector.human papillomavirus type 6b (hpv6b) has been shown to be a major etiologic agent of genital condylomas. the e2 gene, one of the early genes, has been shown to activate the enhancer element in trans in cells transformed with bovine papillomavirus type 1a (bpv1a) but the e2 gene product of any hpv has not been identified. the e2 gene of hpv6b was inserted into the polyhedrin gene of a baculovirus, bombyx mori nuclear polyhedrosis virus (bmnpv), 156 bp downstream from the translational start codon ...19882842232
use of a stable bovine papillomavirus vector to study inducible genes.the human beta interferon (hifn beta 1) gene has been cloned into a bovine papillomavirus type 1 (bpv-1)/pml2 vector. the recombinant dnas can be maintained as stable plasmids in mouse cells, with no detectable rearrangements. the linked hifn beta 1 gene is inducible with little line-to-line variability in independently transformed cell lines. the hifn beta 1 gene is equally induced when it is inserted adjacent to or away from the bpv-1 enhancer. the great stability of the bpv-1/pml2 vector has ...19882842271
initiation of viral dna replication. 19882843015
chromosome aberrations in cattle raised on bracken fern pasture.thirteen cows maintained on natural bracken fern (pteridium aquilinum) were analyzed cytogenetically. the frequency of structural chromosome aberrations detected in peripheral blood cells was significantly higher when compared to that detected in animals raised on pasture containing no bracken fern. we discuss the clastogenic action of fern and its synergistic action with infection by type 2 and 4 papilloma virus in the same animals.19882843400
bovine papillomavirus e2 gene regulates expression of the viral e5 transforming gene.we have performed transient-expression experiments with cv1 monkey kidney cells to investigate the role of the bovine papillomavirus type 1 (bpv1) e2 gene in the regulation of the e5 transforming gene. direct analysis of the 7-kilodalton open reading frame (orf) e5 protein and measurements of the expression of an e5-chloramphenicol acetyltransferase fusion protein indicate that the efficient expression of orf e5 requires the full-length e2 gene, which can be supplied in trans. the viral long con ...19882843663
involvement of human papillomavirus type 8 genes e6 and e7 in transformation and replication.we investigated the transforming activity of human papillomavirus type 8 (hpv8) by expressing all early open reading frames from a heterologous promoter in different rodent fibroblast lines. morphological transformation was observed only in g418-selected mouse c127 and rat 1 cells containing an intact e6-coding region. e6 of hpv8 did not transform nih 3t3 cells as did e6 of bovine papillomavirus type 1. c127 cells transformed by e6 were anchorage independent and had a reduced serum requirement b ...19882843666
bovine papillomavirus type 1 e1 replication-defective mutants are altered in their transcriptional regulation.bovine papillomavirus type 1 (bpv-1) is capable of replicating as a stable, high-copy-number plasmid in transformed rodent cells. the bpv-1 e1 open reading frame (orf) encodes multiple functions involved in viral dna replication. mutations which disrupt the translational integrity of the e1 orf disable the viral genome from replicating as a stable plasmid and result in the integration of the viral genome into the host chromosome generally at a low copy number. despite the low copy number of the ...19882845119
interplay of viral and cellular proteins along the long control region of human papillomavirus type 18.the long control region of human genital papillomavirus type 18 harbors transcription regulatory elements, such as the e6 promoter and a cell type-specific enhancer independent of the e2 protein. by performing dnase i footprint experiments in vitro with protein extracts from different cell lines and tissues we searched for cellular factors interacting with the totality of the control region. we detected a total of eight different protected sites; most of them were found with all the extracts. tw ...19882845145
structure and expression of the guinea-pig alpha-lactalbumin gene.the entire guinea-pig alpha-lactalbumin gene was isolated from a genomic dna library constructed in the bacteriophage lambda l47. the complete nucleotide sequence of the gene and its immediate 5' and 3' flanking sequences were determined and compared with those of the human and rat alpha-lactalbumin genes. this demonstrates that the size, organization and sequence of the exons is highly conserved between species, and reveals the presence of the highly conserved potential regulatory 'milk box' co ...19882845947
the bovine papillomavirus p2443 promoter is e2 trans-responsive: evidence for e2 autoregulation.the bovine papillomavirus type 1 (bpv-1) p2443 promoter is located just upstream of the e2, e3, e4 and e5 open reading frames (orfs) and is active in both transformed rodent cells and in productively infected warts. analysis of viral rna structures suggests that transcripts from this promoter encode the e2 transactivator as well as the e5 oncoprotein. to study expression of p2443, the chloramphenicol acetyltransferase (cat) reporter gene was placed downstream of this promoter, deleting the e2 an ...19882846284
structural and mutational analysis of e2 trans-activating proteins of papillomaviruses reveals three distinct functional domains.the e2 proteins of papillomaviruses are able to transactivate the viral enhancers by interacting with the sequence accgn4cggt found in all papillomavirus long control regions. analysis of the alignment of the amino acid sequences of 10 e2 proteins reveals three distinct regions: two partially conserved domains at the n and c termini of the proteins and a region variable in size and sequence in the middle. a computer prediction of the secondary structure of the 10 sequences outlines interesting c ...19882846285
44-amino-acid e5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids.the 44-amino-acid e5 protein of bovine papillomavirus type 1 is the shortest known protein with transforming activity. to identify the specific amino acids required for in vitro focus formation in mouse c127 cells, we used oligonucleotide-directed saturation mutagenesis to construct an extensive collection of mutants with missense mutations in the e5 gene. characterization of mutants with amino acid substitutions in the hydrophobic middle third of the e5 protein indicated that efficient transfor ...19882847028
changes in dna copy numbers of bovine papillomavirus type 1 after termination of retinoic acid treatment.the number of bovine papillomavirus type 1 (bpv) dna copies [plasmid pdbpv-1 (142-6)] was examined in transformed c127 cells of an riii mouse during exposure to all-trans-retinoic acid (ra) and after its withdrawal. ra treatment of a transformed cell line reduced the number from approximately 60 copies to an average of less than one copy per cell within 5 weeks. the composition of the ra-treated cell population was heterogeneous with respect to bpv dna copies: 89.7% of the cells had no detectabl ...19882848133
efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a bovine papillomavirus/simian virus 40 recombinant virus.to efficiently introduce bovine papillomavirus type 1 genes into cultured cells, we constructed a hybrid viral genome in which the simian virus 40 early region is replaced with a segment of the bovine papillomavirus type 1 transforming region. high-titer stocks of simian virus 40 virions containing the recombinant genome were produced in monkey cells that express simian virus 40 large tumor antigen. cells infected with this virus efficiently expressed the bovine papillomavirus type 1 e2 and e5 g ...19882848252
cutaneous bovine papillomatosis in the sudan: detection of the group-specific virus antigen in warts from affected cattle. 19882848297
mapping of two novel transcripts of bovine papillomavirus type 4.a cdna library was synthesized using rna from bovine papillomavirus type 4 (bpv-4)-induced papillomas. the major viral transcript was characterized by sequencing of its cdna, primer extension mapping and s1 nuclease protection studies. the transcript initiates at multiple sites between nucleotide (nt) 777 and nt 902, contains a splice junction between nt 1016 and nt 3376 and terminates at nt 4034, using the early polyadenylation signal at nt 4009. sequencing of viral cdnas and mrna revealed devi ...19882848926
enhancement of bovine papillomavirus-induced cell transformation by tumour promoters.cultured c3h/10t1/2 cells transfected with the plasmid pdbpv-1 were used as targets, and the frequency of transformed colonies as the endpoint to test the enhancing capacity of four promoters: 12-o-tetradecanoylphorbol-13-acetate (tpa), 4-o-methyl-tetradecanoylphorbol-13-acetate (4-o-methyl-tpa), mezerein and phorbol-12-retinoate-13-acetate (pra). the frequency of the transfected c3h/10t1/2 cells to form transformed colonies was enhanced in the following order: mezerein greater than pra greater ...19882849505
a dimer of bpv-1 e2 containing a protease resistant core interacts with its dna target.the e2 proteins encoded by papillomaviruses interact with the viral dna to regulate its transcription. in the present study, we have constructed bacterial vectors expressing the full-length or n-terminal truncated bpv-1 e2 proteins under the control of an inducible promoter. by uv cross-linking experiments we show that a dimer of the intact or truncated e2 protein interacts with a single palindromic site accgnnnncggt. the dna-binding domain of e2 can be reduced to a small protease resistant core ...19882850174
hepatitis b virus suppresses expression of human beta-interferon.to determine whether hepatitis b virus (hbv) regulates the expression of the human beta-interferon gene, a series of recombinant bovine papilloma virus plasmids containing the human interferon gene and various fragments of the hbv genome were constructed and used to transform c127 cells, a murine fibroblast line. analysis of the dna from transformed c127 cells indicated that the interferon gene was intact and that the plasmids replicated as stable multicopy elements. the 1828-base-pair bamhi hbv ...19882829171
papilloma of the ears of calves following tattooing. 19882851971
the e7 open reading frame of human papillomavirus type 16 encodes a transforming gene.prior analysis of bovine papillomavirus has identified two genes, e5 and e6, which induce morphologic transformation of certain established cells. to study the transforming genes of human papillomavirus (hpv) type 16, the hpv type most commonly associated with cervical carcinoma, we examined subgenomic viral dnas under control of a retroviral long terminal repeat for their capacity to induce cellular transformation of nih 3t3 cells. plasmids carrying the entire viral early region, the e6 and e7 ...19882852339
tumour-associated antigens in primary mouse fibroblasts induced by transformation with bovine papillomavirus type 1.bovine papillomavirus type 1 (bpv 1) dna was used to transform primary fibroblasts of c57bl/6j mice. transformation frequency in these cells was much lower than in c127 cells and not associated with the appearance of morphologically distinct foci. however, continuous lines of transformed c57bl/6j cells were developed by serial subculturing of transfected cells. these transformed cell lines showed phenotypic properties associated with transformation including abnormal karyotypes. they contained v ...19882852603
tumorigenicity of primary mouse fibroblasts transformed by bovine papillomavirus type 1.cell lines transformed by bovine papillomavirus type 1 dna were established from transfected primary fibroblast cultures of c57bl/6 mice. southern blot analysis revealed that most of the viral dna in the cells was in episomal oligomeric form. these cell lines were tested for tumorigenicity in nude mice in comparison to properties associated with malignant transformation including growth in low-serum medium, focus formation in agar, and resistance to natural killer cells. two of the 5 cell lines ...19882852654
expression of an immunoglobulin kappa light-chain gene in lymphoid cells using a bovine papillomavirus-1 (bpv-1) vector.bovine papillomavirus-1 (bpv-1) replicates extrachromosomally in certain murine cell lines, suggesting that vectors based on the bpv-1 replicon might provide a means of obtaining more uniform gene expression among independent transformants. we have tested such a vector for the expression in hybridoma cells of the immunoglobulin kappa light-chain gene, but found that the level of expression varies greatly among transformants. our results also indicate that in these transformants the vector has pr ...19882853103
the genetics of bovine papillomavirus type 1. 19882853608
a novel spontaneous mutation of the bovine papillomavirus-1 genome.a cell clone (cl.2) having an atypical transformed morphology was isolated from a murine c127 cell culture experimentally infected with a bovine papillomavirus type 1 (bpv-1) virion preparation. cl.2 cells exhibited minimal transformed characteristics and contained multiple copies of a bpv-1 plasmid with a molecular size slightly less than that of the wild type viral genome. a simple deletion of 277 bp was mapped to the distal portion of the viral 69% transforming fragment where the early gene r ...19882853880
sequence-specific and general transcriptional activation by the bovine papillomavirus-1 e2 trans-activator require an n-terminal amphipathic helix-containing e2 domain.the sequence-specific trans-activator protein of bovine papillomavirus (bpv)-1, e2, strongly increases transcription at promoters containing papillomaviral accg(n)4cggt (e2p) cis motifs, but can also activate a wide range of co-transfected promoters without e2p cores to a lower extent. analysis of multiple e2 mutants in transfected cells revealed that the c-terminal dna binding e2 domain binds to the e2p cis sequences in the form of pre-existing nuclear dimers. the dna binding function of e2 was ...19882854060
r-loop mapping of rna transcripts from bovine papillomavirus type 4.rna isolated from bovine oesophageal warts was hybridised to bpv-4 genomic dna cloned in a plasmid vector. in r-loop preparations, six major classes of transcripts were mapped. class i, due to an unspliced transcript encompassing the e4/e5 orf region, is most common. in class ii the e4/e5 region is spliced at its 5' end to the e6 orf region, and the rnas appear to have different transcription start points in the e6 orf. some class i r-loops may represent shorter class ii-type transcripts not hyb ...19882855468
a model system for the rescue of cdna encoding transacting transcription activator by contingent replication assay. 19882855627
expression of human epidermal growth factor precursor cdna in transfected mouse nih 3t3 cells.stable cell lines expressing the human epidermal growth factor (egf) precursor have been prepared by transfection of mouse nih 3t3 cells with a bovine papillomavirus-based vector in which the human kidney egf precursor cdna has been placed under the control of the inducible mouse metallothionein i promoter. synthesis of the egf precursor can be induced by culturing the cells in 5 mm butyric acid or 100 microm zncl2. the egf precursor synthesized by these cells appears to be membrane associated; ...19883257563
expression and processing of a recombinant human macrophage colony-stimulating factor in mouse cells.a human macrophage colony-stimulating factor encoded by a 4-kilobase cdna was expressed with bovine papillomavirus vectors in mouse cells. pulse-chase analyses revealed that the 62-kilodalton (kda) translation product was glycosylated, cleaved, and efficiently secreted within 1 h of synthesis. the secreted product contained both n-linked and o-linked oligosaccharide chains. macrophage colony-stimulating factor was present extracellularly as an 80-kda homodimer and as a multimeric species of grea ...19883264878
human growth hormone gene and the highly homologous growth hormone variant gene display different splicing patterns.stably transfected cell lines containing the normal human growth hormone (hgh-n) and human growth hormone-variant (hgh-v) genes have been established in order to study the expression of these two highly homologous genes. each gene was inserted into a bovine papillomavirus shuttle vector under the transcriptional control of the mouse metallothionein gene promoter and the resultant recombinants were transfected into mouse c127 cells. the transfected cells containing the hgh-n gene secrete two hgh ...19883392209
human antibodies react with an epitope of the human papillomavirus type 6b l1 open reading frame which is distinct from the type-common epitope.recombinant proteins encoded by the human papillomavirus type 6b (hpv6b) l1 open reading frame react with sera from patients with condylomata acuminata and also react with rabbit antiserum raised against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (bpv1) virions. to map the immunoreactive epitopes, a series of procaryotic expression plasmids was made which contained a nested set of 3' to 5' deletions in the hpv6b l1 open reading frame. the deleted plasmids expressed a set of ca ...19892463384
demonstration of in vitro synthesis of human papilloma viral proteins from hand and foot warts.hpv particles purified from [35s]-methionine labeled and unlabeled halves of single hand and foot warts have been fractionated into empty, light full, and heavy full particles by buoyant density gradient centrifugation, and their proteins analyzed by two-dimensional gel electrophoresis (ief and nephge) and visualized by either fluorography or silver staining. the l1 coat protein (54 kd) was found in trace amounts in unmodified and slightly modified forms in the labeled empty and light full parti ...19892470829
expression in escherichia coli of seven dna fragments comprising the complete l1 and l2 open reading frames of human papillomavirus type 6b and localization of the 'common antigen' region.molecular cloning was used to express human papillomavirus type 6b (hpv-6b) antigens in escherichia coli. seven genomic dna fragments of hpv-6b which together comprise the complete l1 and l2 open reading frames, known to code for capsid proteins, were cloned and expressed in e. coli as both beta-galactosidase and trpe fusion proteins. western blots of hpv-6b beta-galactosidase fusion proteins using 'genus-specific' antisera produced by immunization of rabbits with disrupted bovine papillomavirus ...19892471790
identification of l2 open reading frame gene products of bovine papillomavirus type 1 using monoclonal antibodies.four hybridoma cell lines producing monoclonal antibodies (mabs) to bovine papillomavirus type 1 (bpv-1) l2 open reading frame (orf) gene products have been established from mice immunized with a bpv-1 l2-beta-galactosidase fusion protein. hybridomas were selected and cloned (from over 700 hybridomas) on the basis of specific reactivity of supernatant fluids with bpv-1 l2 epitopes on disrupted bpv-1 particles and l2-beta-galactosidase fusion proteins by elisa and western blotting, and with aceto ...19892471804
the human papillomavirus type 18 (hpv18) e2 gene product is a repressor of the hpv18 regulatory region in human keratinocytes.the human papillomavirus type 18 (hpv18) long control region (lcr) harbors transcriptional promoter and enhancer elements. recombinant plasmids bearing all or part of the hpv18 lcr cloned in enhancer or promoter configuration upstream of the chloramphenicol acetyltransferase (cat) gene were transfected into human fibroblasts and keratinocytes. although the hpv18 enhancer can function in the absence of e2 gene products in both fibroblasts and keratinocytes, the promoter activity of the hpv18 lcr ...19892476572
tumorigenicity, invasiveness and metastatic capability of fr3t3 rat cells before and after transfection with bovine papilloma virus type 1 dna.fischer rat fr3t3 cells were tested for tumorigenicity, invasive and metastatic capabilities before and after transfection, either with the entire bovine papilloma virus type 1 (bpv-1) genome or with a plasmid (pv69) containing a 69 per cent bam h1-hind iii fragment of the bpv-1 genome as well as bacterial sequences. cell lines were grouped as parental, pv69-transfectants, bpv-1 transfectants, in vitro derivatives, and in vivo derivatives. the tumorigenic, invasive and metastatic capabilities of ...19892535681
open reading frames e6 and e7 of bovine papillomavirus type 1 are both required for full transformation of mouse c127 cells.a series of mutations in open reading frames (orfs) e6 and e7 of bovine papillomavirus type 1 (bpv1) was constructed to analyze the roles of these orfs in transformation of mouse c127 cells. the mutations were designed to prevent synthesis of specific proteins encoded by these genes. none of the mutations caused a decrease in the focus-forming activity of the full-length viral genome or in the ability of the viral dna to replicate as a high-copy-number plasmid. analysis of these mutants in the a ...19892535732
complete nucleotide sequence of the chromosomal gene for human il-4 and its expression.we have isolated a chromosomal dna segment of the human il-4 gene based on homology with a human il-4 cdna sequence and determined its complete nucleotide sequence. the human il-4 gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. it is composed of four exons and three introns and is approximately 10 kilobase pairs in size. 5'-flanking regions of human and mouse il-4 genes share about 85% homology extending more than 500 base pairs upstream of a "tata" like seq ...19892535858
e2 polypeptides encoded by bovine papillomavirus type 1 form dimers through the common carboxyl-terminal domain: transactivation is mediated by the conserved amino-terminal domain.the e2 open reading frame (orf) of bovine papillomavirus type 1 (bpv-1) encodes positive- and negative-acting factors that regulate viral gene expression. the full-length orf encodes a transactivator, and two transcriptional repressors are expressed from the 3' half of the orf. previous analysis has shown that a conserved c-terminal region of 101 amino acids, which is shared by e2 transactivator and repressor proteins, contains the specific dna binding activity. further analysis of the e2 transa ...19892536165
papillomavirus polypeptides e6 and e7 are zinc-binding proteins.papillomavirus proteins e6 and e7 have cys-x-x-cys repeats which have been suggested to mediate zinc binding. we have developed a modification of an assay that detects zinc binding to proteins immobilized on filters. using well-characterized metalloproteins, we show that, under reducing conditions, this assay distinguishes proteins that coordinate zinc through cysteine residues from those that bind the metal through other amino acids. under these conditions, e6 and e7 polypeptides of human papil ...19892536841
the bovine papillomavirus type 1 transcriptional activator e2 protein binds to its dna recognition sequence as a dimer.the transcriptional trans-activator e2 protein from bovine papillomavirus type 1 has been shown to bind to the dna consensus sequence accn6ggt. we have produced the dna-binding domain of the e2 protein as a recombinant protein in escherichia coli. the e2 dna-binding domain was purified as two different molecular weight forms. using these purified proteins, we show that two molecules of the e2 protein bind to a single dna consensus binding site.19892538035
bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cdnas.genetic and biochemical evidence has established that the e2 open reading frame (orf) of bovine papillomavirus type 1 encodes at least two different site-specific dna-binding proteins, one which activates and the other which represses expression from a viral promoter (p. f. lambert, b. a. spalholz, and p. m. howley, cell 50:69-78, 1987). we have obtained data which show that a second form of the repressor gene is expressed in transformed cells harboring stable viral plasmids. the structural deta ...19892538655
identification of bovine papillomavirus e1 mutants with increased transforming and transcriptional activity.the e1 open reading frame of bovine papillomavirus type 1 (bpv) has been shown previously to encode trans-acting functions, m and r, that are involved in extrachromosomal replication of the viral genome. we have determined that several e1 mutants mapping in both the m and r regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse c127 cells than the wild-type genome does. a representative mutant in m, a mutant in r, and the upstream regulatory re ...19892538656
evidence for multiple vegetative dna replication origins and alternative replication mechanisms of bovine papillomavirus type 1.by following up the chance detection in the electron microscope of a dna replication intermediate within a preparation of bovine papillomavirus (bpv-1) dna isolated from purified virus particles, information was obtained about the mechanism of bpv-1 genome replication during the final stages of virus multiplication in naturally infected bovine wart tissue. the structure of viral replication intermediates was investigated by electron microscopic analysis of viral dna linearized by digestion with ...19892539483
loss of bovine papillomavirus dna replication control in growth-arrested transformed cells.the bovine papillomavirus type 1 (bpv-1) genome replicates as a plasmid within the nuclei of bpv-1-transformed murine c127 cells at a constant multiple copy number, and spontaneous amplification of the viral dna is rarely observed. we report here that a mutant bpv-1 plasmid within a contact-inhibited c127 cell line replicated as a stable multicopy plasmid in exponentially growing cells but amplified to a high level in confluent cell culture. in situ hybridization analysis revealed that most of t ...19892539513
mutational analysis of bovine papillomavirus e6 gene.the bovine papillomavirus e6 gene can independently transform mouse c127 cells. to characterize e6 in greater detail, we created 16 site-directed mutations in e6, including substitution mutations in the cysteine codons of the four cys-x-x-cys motifs that are conserved in all papillomavirus e6 proteins. proteins mutated in six of the seven cysteines tested, as well as those lacking the nonconserved c-terminus, were stable in transfected cells but were unable to induce morphological transformation ...19892539522
efficient activation of transcription in yeast by the bpv1 e2 protein.the full-length gene product encoded by the e2 open reading frame (orf) of bovine papillomavirus type 1 (bpv1) is a transcriptional transactivator. it is believed to mediate its effect on the bpv1 long control region (lcr) by binding to motifs with the consensus sequence accn6ggt. the minimal functional cis active site, called the e2 response element (e2re), in mammalian cells comprises two copies of this motif. here we have shown that e2 can function in saccharomyces cerevisiae by placing an e2 ...19892539584
selective enhancement of bovine papillomavirus type 1 dna replication in xenopus laevis eggs by the e6 gene product.genetic analyses of bovine papillomavirus type 1 (bpv-1) dna in transformed mammalian cells have indicated that the e6 gene product is essential for the establishment and maintenance of a high plasmid copy number. in order to analyze the direct effect of the e6 protein on the replication of a bpv-1-derived plasmid, a cdna containing the bpv-1 e6 open reading frame was subcloned into an sp6 vector for the in vitro synthesis of the corresponding mrna. the sp6 e6 mrna was injected into xenopus laev ...19892540419
transcriptional regulation by estrogen of episomal prolactin gene regulatory elements.as a first step in defining the role of chromatin structure in steroid-regulated gene transcription, we have established a steroid-responsive minichromosome system that contains the 5' upstream regulatory region of the rat prl gene (prl) from -10 to -1960-basepairs fused to the antibiotic resistance gene, tn5. the hybrid gene was inserted into a bovine papilloma virus (bpv) vector and then transfected into gh3 cells. southern analysis of total genomic dna revealed that the prl-tn5-bpv dna existe ...19892540428
amplification of specific dna sequences in c127 mouse cells transformed by bovine papillomavirus type 4.a rearranged bovine papillomavirus type 4 dna fragment, present in a line of transformed c127 cells, was molecularly cloned into lambda gt 10. the rearranged viral fragment was found to consist of two separate sequences of 3.8 kb each. clone a comprised 3.3 kb of host dna linked to 0.5 kb of bpv-4 dna. clone b consisted of 2.2 kb of host dna linked to 1.5 kb of bpv-4 dna. the ab locus was found to be amplified and rearranged in a number of different bpv-4 transformed c127 cell lines, irrespectiv ...19892541389
successive steps in the process of immortalization identified by transfer of separate bovine papillomavirus genes into rat fibroblasts.transfer of neor and bovine papillomavirus type 1 (bpv1) dna into rat embryo fibroblasts led to colony formation in g418-containing medium, with no detectable background in controls with neor dna alone. more than 50% of the drug-resistant clones could be further propagated in culture. the genetic functions of bpv1 involved in colony formation and in long-term immortalization were investigated by both translation termination mutations in the full-length genome, which inactivate individual open re ...19892541438
genetic analysis of crpv pathogenesis: the l1 open reading frame is dispensable for cellular transformation but is required for papilloma formation.genetic studies to elucidate the role of papillomaviruses in the development and progression of tumors have been severely hampered because the viruses cannot be grown in tissue culture and therefore mutants are not available. we have employed recombinant dna for papilloma induction to identify essential sequences involved in papillomavirus pathogenesis. here, we demonstrated that deleting most of the open reading frame (orf) l2 did not affect the potential of viral cottontail rabbit papillomavir ...19892541552
the e5 oncoprotein of bovine papillomavirus is oriented asymmetrically in golgi and plasma membranes.the e5 oncoprotein of bpv-1 is a 44 amino acid, hydrophobic polypeptide which is present in membrane fractions of transformed cell homogenates. to define the specific cellular membrane compartments with which e5 associates, immunofluorescence and immunoelectron microscopy were performed using an affinity-purified antibody specific for the e5 carboxyl-terminus. two cell systems which overexpressed the e5 protein were analyzed: (1) balb/c 3t3 mouse cells transformed by a bpv-1 cdna expressing the ...19892541554
expression of hepatitis b virus surface antigen containing the pre-s region in mammalian cell culture system.the surface antigen of hepatitis b virus (hbv) has been expressed in a mouse cell line using metallothionein-bovine papilloma virus vectors. four different recombinant plasmids were used and it was found that the expression level varies significantly from one plasmid to another. removing the hbv polyadenylation signal from the plasmid drastically reduced the expression level. providing even a heterologous polyadenylation signal improved the expression level from the reduced one by at least tenfo ...19892541576
specific recognition nucleotides and their dna context determine the affinity of e2 protein for 17 binding sites in the bpv-1 genome.the dna context of nucleotides that a protein recognizes can influence the strength of the protein-dna interaction. moreover, in prokaryotes, understanding the quantitative differences in binding affinities that result in part from the dna context is often important in describing regulatory mechanisms. nevertheless, these issues have not been a major focus yet for the investigation of protein-dna interactions in eukaryotes. in this study, we explored the binding specificity and the range of affi ...19892542129
genetic assignment of multiple e2 gene products in bovine papillomavirus-transformed cells.the e2 open reading frame of bovine papillomavirus type 1 has been shown genetically to encode at least three transcriptional regulatory factors, and three e2 specific proteins have been recently identified in virally transformed rodent cells. in this study, the genes encoding these e2 specific proteins have been determined. the 48-kilodalton (kda) protein was identified as the product of a full-length e2 open reading frame cdna, which confirmed that this polypeptide is the e2 transactivator. th ...19892542621
cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome.tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the bpv-1 genome was found to involve distinct proliferative stages. cell cultures derived from normal skin, from benign proliferative fibromatoses, and from malignant fibrosarcomas each evidenced distinguishable, cell-heritable characteristics. the latent viral genome was transcriptionally inactive in normal-appearing skin and was activated in the dermal fibromatoses. fibrosarcoma cells grew continuously in culture, forme ...19892542769
multiple cooperative interactions constrain bpv-1 e2 dependent activation of transcription.transcription directed by the bpv-1 long control region (lcr) is conditional upon activation by the virally encoded e2 protein. within the 1.0 kb lcr there are five separate regions, a to e, that contain e2 responsive enhancers. the smallest functional region, a, is only 38 bp and contains two copies of the consensus sequence acc(n)6ggt that is known to function as an e2 binding site in vitro. we show that a pair of these constitutes a minimal functional e2 responsive enhancer element but that t ...19892542891
expression of epstein-barr virus membrane antigen gp340/220 in mouse fibroblasts using a bovine papillomavirus vector.epstein-barr virus (ebv) membrane antigen glycoproteins gp340 and gp220 are encoded by a single gene. we have inserted this gene into a bovine papillomavirus (bpv) vector and expressed gp340/220 in mammalian cells under the control of the mouse metallothionein promoter. the proteins produced were of similar mr, showed similar antigenic specificity and were transported to the same subcellular location as the authentic gp340/220. the inclusion of heavy metal ions in the medium had no effect on the ...19892543757
the effect of bovine herpesvirus type 1 glycoproteins gi and giii on herpesvirus infections.we expressed the bovine herpesvirus type 1 (bhv-1) glycoproteins, gi and giii, in bovine cells using a bovine papillomavirus vector. the proteins expressed by these cells had the same mr as the native bhv-1 proteins and monoclonal antibodies detected no differences in their antigenic structure. cells expressing gi were infected with either bhv-1 or herpes simplex virus type 1 (hsv-1). the number of plaques in gi-expressing cells was similar to that seen with normal fibroblasts infected with bhv- ...19892543789
characterization of bovine papillomavirus type 1-transformed clones which show distinct transformed phenotypes.seventeen independent cell clones were isolated from c127 cells transformed by bovine papillomavirus type 1 (bpv-1). transformants showed differing degrees of expression of the transformed phenotype as monitored by saturation density, doubling time, growth in medium with a low serum concentration and colony-forming efficiency in soft agar. the degree of expression of the transformed phenotype did not correlate with either the bpv-1 copy number or levels of bpv-1-specific rna in the transformed c ...19892543792
specific chromosomal abnormalities characterize fibrosarcomas of bovine papillomavirus type 1 transgenic mice.in the bpv1.69 line of transgenic mice, the bovine papillomavirus type 1 genome elicits both benign dermal fibroblastic proliferation (fibromatoses) and malignant fibrosarcomas. because these lesions arise only with time, nonviral factors appear to be involved. we have karyotyped several primary tumors as well as a series of low-passage cell lines derived both from fibromatoses and from fibrosarcomas. the fibrosarcomas, but not the preneoplastic fibromatoses, show consistent abnormalities of one ...19892544888
identification and characterization of the bpv-2 l2 protein.the bovine papilloma virus type 2 (bpv-2) l2 open reading frame was cloned into a lambda pl promoter expression vector. this plasmid was shown to express a fusion protein which constituted 75% of the bpv-2 l2 orf linked to the first 13 n-terminal amino acids of the lambda cll gene product. antisera generated against this fusion protein were used to identify the l2 gene product as a 64,000-da protein in bpv-2 virions. western blot analysis demonstrated that the l2 viral protein was present in ful ...19892545035
infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection.papillomavirus dna has been reported recently in the vapor (smoke plume) derived from warts treated with carbon dioxide laser; this raises concerns for operator safety. we therefore have studied a group of human and bovine warts to define further the potential risk of wart therapy and to test whether a surgical mask could reduce exposure. half of each wart was treated with carbon dioxide laser and the other half with electrocoagulation. the vapor produced by each form of therapy was collected wi ...19892545749
transcriptional termination between bovine papillomavirus type 1 (bpv-1) early and late polyadenylation sites blocks late transcription in bpv-1-transformed cells.bovine papillomavirus type 1 (bpv-1) is a small dna tumor virus which induces fibropapillomas in cattle and transforms rodent cells in culture. transcripts are derived from a single strand of the circular viral genome, which has multiple promoters and two polyadenylation sites. in the transformed cell, the first (early) polyadenylation site is utilized exclusively and, therefore, only the early region is expressed. transcription of the late genes, which requires use of the second (late) polyaden ...19892545923
dual loci of dna bending in the bovine papillomavirus upstream regulatory region.recombinant clones containing all or portions of the bovine papillomavirus (bpv) upstream regulatory region (urr) were constructed. when analyzed by polyacrylamide gel electrophoresis, the cloned urr sequences exhibited electrophoretic properties characteristic of dna containing bend sites. two distinct bend centers were identified, mapping to approximately 7477 and 7790 respectively on the bpv genome. no other loci of static dna bending were detected in the urr region of the bpv genome.19892546330
stably expressed fipv peplomer protein induces cell fusion and elicits neutralizing antibodies in mice.we have established bovine papilloma virus (bpv)-transformed mouse c127 cell lines that synthesize the peplomer protein of the feline infectious peritonitis virus (fipv) strain 79-1146. for this purpose, a new cassette expression vector phsl, which carries the drosophila hsp70 promotor and the polyadenylation signal of the moloney murine leukemia virus long terminal repeat, was constructed. cocultivation of the bpv-transformed cell lines with fipv-permissive feline fcwf-d cells resulted in polyk ...19892548329
bovine papilloma virus encoded e2 protein activates lymphokine genes through dna elements, distinct from the consensus motif, in the long control region of its own genome.activation of t cells by antigen, lectin or a combination of phorbol ester (pma) and calcium ionophore (a23187) leads to the induction of a set of lymphokine genes. transfection of a human t cell leukemia cell line, jurkat, or an african green monkey kidney cell line, cv1, with a cdna encoding e2 protein, a trans-activator of bovine papilloma virus type 1, results in activation of interleukin 2 (il-2), interleukin 3 (il-3) and granulocyte/macrophage colony-stimulating factor (gm-csf) genes in a ...19892548843
papillomavirus-associated inductions of cellular proteins in mouse c127 cells: correlation with the presence of open reading frame e2.bovine papillomavirus type 1 (bpv-1) readily transforms mouse c127 cells, conferring the ability to grow in soft agar and to form tumors in athymic (nu/nu) mice. electrophoresis of total cellular proteins from these bpv-transformed lines on ultra-high resolution, giant two-dimensional gels displays the presence of novel, papillomavirus-related protein phenotypes. analysis of the established bpv-1-transformed c127 cell lines, id13 and id14, reveals a set of six proteins which are either absent or ...19892549708
the adeno-associated virus rep78 gene inhibits cellular transformation induced by bovine papillomavirus.adeno-associated virus type 2 (aav) is a helper dependent parvovirus which can inhibit the oncogenic and transforming potential of its helper viruses: adenoviruses (ad) and herpesviruses. here we have assayed aav's ability to inhibit cellular transformation induced by bovine papillomavirus type 1 (bpv-1), a member of another family of dna viruses. aav was able to markedly inhibit bpv-1-induced transformation of contact-inhibited murine fibroblasts either by infection with virus particles or by d ...19892549714
amplification of bovine papillomavirus dna by n-methyl-n'-nitro-n-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus.treatment with n-methyl-n'-nitro-n-nitrosoguanidine (mnng) or irradiation with ultraviolet light (uv254 nm) induces amplification of integrated as well as episomal sequences of bovine papillomavirus (bpv) type 1 dna in bpv-1-transformed mouse c127 cells (i.e., id13 cells). this is shown by filter in situ hybridization and southern blot analysis of cellular dna. similarly, infection of id13 cells with herpes simplex virus (hsv) type 1 which has been shown to be mutagenic for host cell dna leads t ...19892549724
animal virus dna replication. 19892549858
trans activation by the bovine papillomavirus e2 protein in saccharomyces cerevisiae.the papillomavirus e2 protein functions as an enhancer-binding factor to promote transcription in mammalian cells. we found that one copy of the e2 binding site acted as an e2 protein-dependent upstream activating sequence in saccharomyces cerevisiae. additional copies of the binding motif further augmented transcription. these results imply that the e2 protein functionally interacts with highly conserved transcriptional elements.19892550673
independent glucocorticoid induction and repression of two contiguous responsive genes.specific dna sequence elements which contain binding sites for the glucocorticoid receptor mediate the action of glucocorticoid hormones on gene transcription. in glucocorticoid-inducible genes, these glucocorticoid-responsive elements behave as hormone-inducible enhancers of transcription. we have taken advantage of the bovine papillomavirus (bpv) system to test the stringency of glucocorticoid regulation of transcription. bpv episomes were constructed to contain two hormone-regulated transcrip ...19892550796
the bovine papillomavirus e5 transforming protein can stimulate the transforming activity of egf and csf-1 receptors.the bovine papillomavirus e5 transforming gene encodes a 44 amino acid protein product that is localized to cytoplasmic membranes, including the plasma membrane. we now report that e5 can cooperate with human egf receptors and with human csf-1 receptors to induce cellular transformation of nih 3t3 cells. cooperation occurred in the absence of receptor stimulation by ligand, and it was further augmented by treatment with ligand. cooperation was not seen between e5 and either c-fes or c-src. the c ...19892551505
structure, activity, and regulation of the bovine papillomavirus e5 gene and its transforming protein product. 19892551579
transforming activity of a 16-amino-acid segment of the bovine papillomavirus e5 protein linked to random sequences of hydrophobic amino acids.the 44-amino-acid e5 protein of bovine papillomavirus type 1 is the smallest transforming protein yet described. previous results from our laboratory indicate that a hydrophobic core and specific carboxyl-terminal amino acids are required for the e5 protein to exert its transforming function. in this study, additional substitution mutations were generated in the e5 gene to determine the minimal amino acid sequence requirements for focus formation in mouse c127 cells. in most cases examined, subs ...19892552136
mutational analysis of bovine papillomavirus type 1 e5 peptide domains involved in induction of cellular dna synthesis.early gene e5 of bovine papillomavirus type 1 encodes a 44-amino-acid protein whose expression can transform immortalized mouse cell lines. we have previously reported that a chemically synthesized e5 peptide functions to induce cellular dna synthesis upon microinjection into growth-arrested mouse cells. we further defined the two e5 domains essential for the full dna synthesis induction activity by the analysis of e5 deletion and amino acid substitution mutant peptides. the first domain is the ...19892552177
nutritional requirements of papillomavirus-transformed mouse cells and an uninfected parent line in serum-free culture.a serum-free culture system was used to compare the nutritional requirements of mouse mammary cells transformed by bovine papillomavirus type 1 (id13 cells) and the uninfected parent line (c127 cells). the serum-free, chemically defined medium used for this study was an mcdb 151-based medium (mcdb 151+s+i), supplemented with epidermal growth factor, transferrin, hydrocortisone, ethanolamine, phosphoethanolamine, retinoic acid, trace metals, and insulin. proliferation of either cell type in serum ...19892553658
the e2 trans-activating protein of bovine papillomavirus type 1 (bpv1) is serine-phosphorylated in vivo.the e2 open reading frame of bovine papillomavirus 1 (bpv1) encodes both positive and negative transcriptional regulatory factors. the full-length e2 gene polypeptide is a strong transcriptional transactivator that acts on enhancers within the papillomavirus long control region (lcr), and two shorter e2 proteins function as transcription repressors. a vaccinia recombinant virus harboring the full length e2 coding sequence of bpv1 directs the synthesis of a 48 kd phosphoprotein with specific dna ...19892554235
induction of virus-producing tumours in athymic nude mice by bovine papillomavirus type 4.bovine papillomavirus type 4 (bpv-4), the causative agent of alimentary papillomatosis, has been used to infect, in vitro, fragments of palatine mucosa from late term bovine fetuses. these small explants were placed beneath the renal capsule of athymic nude mice where they grew to produce, at first, squamous epithelial cysts containing bpv-4 genomic dna and, later, papillomas which were morphologically identical to those of cattle and which contained large amounts of replicating virus. the possi ...19892554558
suppression of focus formation by bovine papillomavirus-transformed cells by contact with non-transformed cells: involvement of sugar(s) and phosphorylation.focus formation by bovine papilloma virus-transformed c127 cells was inhibited by direct contact with non-transformed c127 cells. the suppressive capacity of c127 cells was abolished by introduction of the neomycin resistance gene (neor) but not by that of the hygromycin resistance gene (hygrr). though both genes code for phosphotransferase which inactivates the aminoglycoside antibiotics, their substrates are different, i.e., there is no cross-resistance between them. as the neomycin phosphotra ...19892555308
inducible expression of encephalomyocarditis virus 3c protease activity in stably transformed mouse cell lines.an inducible expression vector system has been developed to facilitate the study of the effects of individual virus gene products on cell function. the vector utilizes the mouse metallothionein promoter carried on the bovine papillomavirus genome. conditions which optimize the induced expression of open reading frames inserted downstream from the mouse metallothionein promoter have recently been described. in this communication we describe the use of this system to clone and express the encephal ...19892555538
phosphorylation sites of the e2 transcriptional regulatory proteins of bovine papillomavirus type 1.the e2 open reading frame of bovine papillomavirus type 1 (bpv-1) encodes three transcriptional regulatory proteins. the full-length open reading frame encodes a protein of 410 amino acids which functions as a transcriptional transactivator. two transcriptional repressor proteins, e2-tr and e8/e2, contain the c-terminal 249 and 204 amino acids, respectively. we have expressed both the full-length e2 protein and the e2-tr repressor protein in insect cells, by using recombinant baculoviruses, and ...19892555544
genetic evidence that acute morphologic transformation, induction of cellular dna synthesis, and focus formation are mediated by a single activity of the bovine papillomavirus e5 protein.the bovine papillomavirus (bpv) type 1 e5 gene encodes a 44-amino-acid protein that can stably transform cultured rodent cells when expressed in the absence of all other viral genes. we have previously constructed a bpv-simian virus 40 recombinant virus (pava-1) which efficiently expresses the bpv type 1 e5 gene in infected cells (j. settleman and d. dimaio, proc. natl. acad. sci. usa 85:9007-9011, 1988). within 48 h of pava-1 infection, the vast majority of mouse c127 cells underwent a dramatic ...19892555701
purification and dna-binding properties of human papillomavirus type 16 e6 protein expressed in escherichia coli.unfused human papillomavirus type 16 (hpv 16) e6 protein was expressed in escherichia coli using a lambda pl promoter system. the protein was isolated from the cells as inclusion bodies, extracted by 6 m guanidine-hcl, and purified by chromatography. the purified protein had high affinity to dna and was demonstrated for the first time to bind to a specific sequence within the long control region of hpv 16.19892556128
complex formation of human papillomavirus e7 proteins with the retinoblastoma tumor suppressor gene product.the e7 proteins encoded by the human papillomaviruses (hpvs) associated with anogenital lesions share significant amino acid sequence homology. the e7 proteins of these different hpvs were assessed for their ability to form complexes with the retinoblastoma tumor suppressor gene product (p105-rb). similar to the e7 protein of hpv-16, the e7 proteins of hpv-18, hbv-6b and hpv-11 were found to associate with p105-rb in vitro. the e7 proteins of hpv types associated with a high risk of malignant pr ...19892556261
injection of xenopus eggs before activation, achieved by control of extracellular factors, improves plasmid dna replication after activation.injection of molecular probes into unfertilized xenopus eggs requires suppression of activation. but the unfertilized egg is poised for activity, and pricking, like sperm penetration, triggers the start of the first cell cycle. methods of suppressing activation generally rely on introduction of drugs into the cell, but some of these techniques are irreversible. i report here that injection without activation can also be accomplished by simply limiting extracellular free ca2+ to 1-2 microm. the s ...19892559091
[using bpv transforming foci as selective markers to express hbsag].we constructed a plasmid pbmthbr2 containing mouse mt promoter, entire hbsag gene (pres and s gene), splicing signal from sv40 and complete bpv genome. using calcium phosphate precipitation technique to transform c127 cells and using bpv transforming foci as selective markers, we obtained transformed cell clones. the experiment shows that 57% of the cloned cell lines can secrete hbsag continuously.19892561512
bovine papillomavirus type i induces resistance to ca+(+)-induced terminal differentiation in murine keratinocytes.bovine papillomavirus type 1 (bpv-1) was expressed in established mouse balb/mk epidermal keratinocytes. in each of the transfected cell lines, dna synthesis was stimulated by epidermal growth factor (egf) and inhibited by type beta transforming growth factor to an extent similar to that in parental cells. in contrast, the bpv-1-transfectants were resistant to the induction of terminal differentiation by extracellular ca(+)+. first, bpv transfectants continued to respond to egf in the presence o ...19892561735
tumorigenic latency and separable stages during fibrosarcoma development in transgenic mice carrying papillomavirus genomes.transgenic mice have been established carrying the genomes of bovine papillomavirus type 1 (bpv-1), and human papillomaviruses types 5 and 18. transcriptional dormancy is characteristic of all three viral genomes in transgenic mouse lines maintained for 2-4 years. only bpv-1, which induces both dermal and epidermal pathology in its natural host, has been found to elicit abnormalities when carried in transgenic mice. the bpv-1 genome acts in these mice as a tissue specific oncogene, in that it el ...19892562186
promoting activity of betel quid ingredients and their inhibition by retinol.ingredients of betel quids, which have been linked to the high incidence of precancerous oral lesions and oral cancers, were examined for their promoting activity. aqueous extracts were tested using the bovine papillomavirus (bpv) dna transformation assay, which consists of cultured c3h/10t1/2 cells transfected with the plasmid pdpbv-1 as targets, and the frequency of transformed foci as endpoints. areca nut extracts enhanced the formation of bpv dna-induced transformed foci approximately tenfol ...19892713825
the e5 oncoprotein of bovine papillomavirus binds to a 16 kd cellular protein.the e5 oncoprotein of bovine papillomavirus type 1 is the smallest known viral transforming protein. it is a 44 amino acid polypeptide asymmetrically oriented in golgi and plasma membranes which appears to modify (either directly or indirectly) the internalization and phosphorylation of at least two growth factor receptors: egf and csf-1. to identify cellular proteins associated with e5, we have constructed two e5 fusion proteins, each of which contains a well-characterized epitope at the e5 ami ...19901688529
a monoclonal antibody to ly-6 gene product inhibits generation of functionally active t cells and recognizes single antigenic specificity whose expression is up-regulated in virus-transformed rat fibroblast.in order to elucidate the relationship between the structure and function of proteins encoded for by the ly-6 gene complex, a cdna was constructed for a ly-6.2 specificity and then monoclonal antibodies (mab) generated to bacterially synthesized protein. the addition of one of these mab, designated pb-19, inhibited the proliferative response of t cells to concanavalin a (con a) or major histocompatability complex (mhc) alloantigens. reactivity of pb-19 to the ly-6 specificity was blocked by a kn ...19901692303
antibody-mediated neutralization in vivo of infectious papillomaviruses.specific antibody-mediated neutralization of infectious human papillomavirus type 11 (hpv-11) was achieved in the athymic mouse xenograft system, in which hpv-11 induced morphological transformation of human foreskin. virus-specific neutralization was demonstrated by the ability of an hpv-11-specific polyclonal antiserum to neutralize hpv-11 infectivity and not bovine papillomavirus type 1 (bpv-1) or cottontail rabbit papillomavirus (crpv) infectivity. in all three virus infectivity systems, neu ...19901693698
distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides.monoclonal (mabs) and polyclonal antibodies were produced against the major capsid protein of detergent-disrupted, purified bovine papillomavirus type 1 (bpv-1). the precise locations of the corresponding epitopes were identified by the reactivity of mabs and selected polyclonal antibodies with synthetic, overlapping, hexameric peptides corresponding with 95% of the bpv-1 major capsid protein. the topography of these epitopes was determined by reactivity of antibodies with intact (conformational ...19901700026
demonstration of evolutionary differences between conserved antigenic epitopes in the minor nucleocapsid protein of human papillomavirus types 6b, 16 and 18.we studied human papillomavirus (hpv) minor nucleocapsid protein (l2) by epitope scanning. conserved antigenic epitopes identified by rabbit antiserum to bovine papillomavirus (bpv) were revealed in hpv-6b (amino acids, aa, 196-205); hpv-16 (aa:s 376-85) and hpv-18 (aa:s 221-230). l2 proteins. the first two epitopes were situated in hydrophilic regions of the proteins. aligning the aa-sequences that corresponded to the epitopes with the total l2 sequences of bpv and hpv1a revealed consensus moti ...19901700908
an interaction between the 5' flanking distal and proximal regulatory domains of the rat prolactin gene is required for transcriptional activation by estrogens.in vitro studies have demonstrated that the estrogen receptor (er) can bind to the rat prl estrogen response element (ere) located 1700 basepairs upstream of the transcriptional start site. however, the mechanism by which the receptor-dna complex influences the activity of rna polymerase located in the promoter region is not understood. to begin investigating this process, we developed cell lines derived from gh3 cells that contain steroid-responsive bovine papillomavirus minichromosomes. within ...19901963474
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