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two e2 binding sites (e2bs) alone or one e2bs plus an a/t-rich region are minimal requirements for the replication of the human papillomavirus type 11 origin.human papillomaviruses (hpvs) cannot be propagated in vitro, but the dna can be replicated transiently in an assay in the presence of two trans-acting viral proteins, e1 and e2. using this assay, we have defined the minimal cis-acting elements of the origin of replication of hpv type 11. most hpv genomes are conserved at the origin of replication, and the core contains three e2 binding sites (e2bs) surrounding an a/t-rich spacer region. the present results show that the minimal requirement for r ...19938230435
the human t-cell leukemia/lymphotropic virus type i p12i protein cooperates with the e5 oncoprotein of bovine papillomavirus in cell transformation and binds the 16-kilodalton subunit of the vacuolar h+ atpase.the human t-cell leukemia/lymphotropic virus type i (htlv-i) induces t-cell leukemia and transforms human t cells in vitro. a recently identified protein with a molecular weight of 12,000 (12k) (p12i), encoded by single- and double-spliced mrnas transcribed from the 3' end of the htlv-i genome, has been shown to localize in the perinuclear compartment and in the cellular endomembranes. the p12i protein exhibits significant amino acid sequence similarity to the e5 oncoprotein of bovine papillomav ...19938230493
enrichment for metallothionein does not confer resistance to cisplatin in transfected nih/3t3 cells.evidence has been presented both that metallothionein does and does not produce resistance to cisplatin. the metallothionein-enriched cells described in most previous studies have been selected for resistance to heavy metals, such as cadmium, or have been maintained in a medium enriched for the metals. exposure to toxic metals could alter the cells in many ways. this report addresses the effect of metallothionein content alone, independent of exposure to metals, on cellular resistance to cisplat ...19938246143
site-specific dna-binding proteins important for replication and transcription have multiple activities. 19937956054
site-specific initiation of dna replication in metazoan chromosomes and the role of nuclear organization.we have asked whether or not xenopus eggs or egg extracts, which have previously been shown to replicate essentially any dna molecule, will preferentially utilize a known mammalian obr. our results reveal that xenopus egg extracts can preferentially initiate dna replication at sites chosen in vivo by the hamster cell, provided that the dna substrate is presented to the extract in the form of a nucleus rather than bare dna. thus, site-specific initiation of dna replication in metazoan cell chromo ...19937956062
protein-sulfenic acid stabilization and function in enzyme catalysis and gene regulation.sulfenic acids (r-soh) result from the stoichiometric oxidations of thiols with mild oxidants such as h2o2; in solution, however, these derivatives accumulate only transiently due to rapid self-condensation reactions, further oxidations to the sulfinic and/or sulfonic acids, and reactions with nucleophiles such as r-sh. in contrast, oxidations of cysteinyl side chains in proteins, where disulfide bond formation can be prevented and where the reactivity of the nascent cysteine-sulfenic acid (cys- ...19938262333
mapping of linear b cell epitopes on capsid proteins of bovine papillomavirus: identification of three external type-restricted epitopes.immunodominant, conserved and type-restricted external epitopes of bovine papillomavirus (bpv) major (l1) capsid protein have been identified using bpv particles and synthetic peptides. antisera to disrupted bpv-1 recognized bpv-1 and bpv-2 particles in immune electron microscopy (iem) studies and inhibited bpv-2-induced focus formation of nih/3t3 cells. thus bpv-1/bpv-2 cross-reactive epitopes occur on the surface of virions. the l1 protein appeared to be immunodominant as the antisera reacted ...19938277272
platelet-derived growth factor receptor can mediate tumorigenic transformation by the bovine papillomavirus e5 protein.we showed previously that the beta receptor for platelet-derived growth factor (pdgf) is constitutively activated in fibroblasts transformed by the 44-amino-acid bovine papillomavirus type 1 (bpv) e5 protein and that the e5 protein and the pdgf receptor exist in a stable complex in e5-transformed fibroblasts. on the basis of these results, we proposed that activation of the pdgf receptor by the bpv e5 protein generates a sustained proliferative signal, resulting in fibroblast transformation. in ...19938321218
papillomavirus e7 protein binding to the retinoblastoma protein is not required for viral induction of warts.human papillomaviruses (hpvs) are the etiologic agents responsible for benign epithelial proliferative disorders including genital warts and are a contributory factor in the pathogenesis of cervical cancer. hpvs demonstrate strict species and cell-type specificity, which is manifested by the inability of these viruses to induce disease in any species other than humans. the natural history of hpv infection in humans is closely mimicked by cottontail rabbit papillomavirus (crpv) infection in domes ...19938380462
bovine papilloma virus (bpv)-encoded e1 protein contains multiple activities required for bpv dna replication.replication of bovine papilloma virus (bpv) dna requires two virus-encoded proteins, e1 and e2, while all other proteins are supplied by the host cell. here, we describe the isolation of the e1 protein and show that it is a multifunctional protein. purified e1 protein was required for the in vitro replication of bpv origin-containing dna by extracts of mouse cells, as reported [yang, l., li, r., mohr, i. j., clark, r. & botchan, m. r. (1991) nature (london) 353, 628-632]. in addition, the e1 pro ...19938380645
bpv-4 induces amplification and activation of 'silent' bpv-1 in a sub-line of c127 cells.bpv-4-induced malignant transformation of c127 mouse fibroblasts in vitro is the result of a 'hit and run' mechanism. viral dna is lost on continued subculture of transformed cell lines without loss of any malignant characteristics. the dna from these cells harbours specific amplified sequences. two such amplified fragments of approximately 10 kb and 12 kb were molecularly cloned and designated hl-10 and hl-12 respectively. hl-10 transformed c127 cells efficiently and therefore encodes a transfo ...19938380914
the bovine papillomavirus origin of replication requires a binding site for the e2 transcriptional activator.the bovine papillomavirus type i transcriptional activator e2 is essential for replication of bovine papillomavirus dna, yet most of the high-affinity binding sites for e2 are dispensable. here we demonstrate an absolute requirement for a binding site for the e2 polypeptide as a cis-acting replication element, establishing that site-specific binding of e2 to the origin is a prerequisite for bovine papillomavirus replication in vivo. the position and distance of the e2 binding site relative to th ...19938381536
the e1 replication protein of bovine papillomavirus type 1 contains an extended nuclear localization signal that includes a p34cdc2 phosphorylation site.bovine papillomavirus (bpv) dna replication occurs in the nucleus of infected cells. most enzymatic activities are carried out by host cell proteins, with the viral e1 and e2 proteins required for the assembly of an initiation complex at the replication origin. in latently infected cells, viral dna replication occurs in synchrony with the host cell chromosomes, maintaining a constant average copy number of bpv genomes per infected cell. by analyzing a series of mutants of the amino-terminal regi ...19938382303
regulation of the human papillomavirus type 11 e6 promoter by viral and host transcription factors in primary human keratinocytes.human papillomavirus (hpv) type 11 is strictly trophic for epithelial cells and induces benign condylomata of the external genitalia and also causes laryngeal papillomas. primary keratinocytes are the appropriate hosts for studies of hpv gene regulation, but they are not frequently used, owing to difficulties in culturing and low transfection efficiencies. by modifying a polybrene transfection procedure, we achieved consistently high transfection efficiencies in primary human foreskin keratinocy ...19938382318
binding of bovine papillomavirus e1 to the origin is not sufficient for dna replication.replication of the bovine papillomavirus (bpv-1) dna requires both the viral e1 and e2 gene products. the minimal origin of replication, which resides in a 60-basepair fragment centered on the unique hpai site of the bpv-1 genome, can be bound by the e1 protein and is flanked by e2 binding sites. the integrity of the region surrounding the unique hpai restriction enzyme site is important for e1 binding and dna replication, but the e2 binding sites are not required. the ability of e1 to complex w ...19938382395
in situ hybridisation of equine sarcoids with bovine papilloma virus. 19938383371
in vitro evaluation of phosphorothioate oligonucleotides targeted to the e2 mrna of papillomavirus: potential treatment for genital warts.papillomaviruses induce benign proliferative lesions, such as genital warts, in humans. the e2 gene product is thought to play a major role in the regulation of viral transcription and dna replication and may represent a rational target for an antisense oligonucleotide drug action. phosphorothioate oligonucleotides complementary to e2 mrnas were synthesized and tested in a series of in vitro bovine papillomavirus (bpv) and human papillomavirus (hpv) models for the ability to inhibit e2 transacti ...19938383937
analysis of the transforming functions of bovine papillomavirus type 4.bovine papillomavirus type 4 (bpv-4) morphologically transforms primary bovine cells in vitro only in the presence of an activated ras gene. the transformed cells are capable of anchorage-independent growth, but are not immortal and are incapable of inducing tumors in nude mice. bpv-4 does not possess an e6 orf and failure to induce full transformation may be due to the lack of this gene. here we report the contribution of individual bpv-4 genes to cell transformation and the effect of adding th ...19938384749
bovine papilloma virus (bpv)-encoded e2 protein enhances binding of e1 protein to the bpv replication origin.the replication of bovine papilloma virus (bpv) dna in vivo requires two viral-encoded proteins, e1 and e2, while all other proteins are derived from the host. we described previously the isolation of the e1 protein and showed that it contains multiple functions required for bpv dna replication. the bpv transcription factor e2 was shown by others to stimulate bpv dna replication in vitro. here, we present results that account for the role of the e2 protein. the e1 protein bound selectively to th ...19938385347
sites of predicted stress-induced dna duplex destabilization occur preferentially at regulatory loci.this paper describes a computational method to predict the sites on a dna molecule where imposed superhelical stresses destabilize the duplex. several dna sequences are analyzed in this way, including the pbr322 and cole1 plasmids, bacteriophage f1, and the polyoma and bovine papilloma virus genomes. superhelical destabilization in these molecules is predicted to occur at small numbers of discrete sites, most of which are within regulatory regions. the most destabilized sites include the termina ...19938385354
identification of proteins binding to the f441 locus of polyomavirus b enhancer that are required for its activity in embryonic carcinoma cells.a point mutation at nucleotide 5233 of the polyomavirus (a2 strain) enables it to overcome growth restriction in undifferentiated embryonal carcinoma cells. we analysed the binding of nuclear proteins from f9 cells to a 38 bp region that spans this site of mutation and encompasses two copies of the bovine papillomavirus core sequence, ccaccc, and characterized this domain by mutational analysis. our results showed that the f441 mutation creates a sequence motif which binds tef-1 or a tef-1-like ...19938385690
synthesis and assembly of infectious bovine papillomavirus particles in vitro.bovine papillomavirus type 1 (bpv-1) virions were produced in vitro using vaccinia virus (vv) recombinants expressing the bpv-1 l1 and l2 capsid proteins. particles morphologically resembling papillomaviruses were observed in the nucleus of cells infected with a vv recombinant for the bpv-1 l1 protein, and greater numbers of similar particles were seen in the nuclei of cells infected with a vv double recombinant for l1 and l2. virus-like particles (vlps) assembled in cells infected with the vv d ...19938385700
characterization of human papillomavirus type 11 e1 and e2 proteins expressed in insect cells.the study of human papillomavirus replication has been hampered by the lack of an in vitro system which reliably supports virus replication. recent results from the bovine papillomavirus (bpv) system indicate that the e1 and e2 proteins are the only viral gene products required for replication. by analogy with simian virus 40 large t antigen, e1 is thought to possess atpase and helicase activity, which may play a direct role in viral dna replication. the precise role of e2 is unclear, but it may ...19938386271
the 23-kilodalton e1 phosphoprotein of bovine papillomavirus type 1 is nonessential for stable plasmid replication in murine c127 cells.the 23-kda protein encoded by the 5' segment of the e1 open reading frame of bovine papillomavirus type 1 (bpv1) was previously ascribed a negative regulatory function for the replication of viral plasmid dna. however, results from recent functional and biochemical studies do not readily support this genetic assignment. therefore, we have reassessed the role of this protein in papillomavirus dna replication by using a mutant of bpv1 which is unable to express this e1 protein. this mutant viral d ...19938386283
t2g4 telomere repeats does not provide telomere function to a bpv-1 containing dna fragment in mouse c127 cells.the ability of the (t2g4)n telomeric repeats to maintain a linear structure in an extrachromosomal replicating plasmid in mouse c127 cells was tested in a vector based on bovine papillomavirus type-1, ars, his3 and the neo genes. digestion with bamhi releases a bpv-1 containing fragment with a (t2g4)n repeats at each end which was introduced to yeast and microinjected into mouse c127 cells. while the linear construct was maintained as extrachromosomal structure in yeast cells, none of the result ...19938387849
behaviour of plasmid containing c4a2 repeats in s. cerevisiae and s. pombe.plasmid, which combined the complete genome of bpv-i, yeast ars, leu yeast selectable marker gene, the neo selectable marker gene and inverted (c4a2)n telomeric repeat gene sequences cloned originally from tetrahymena thermophila, was constructed. it was introduced in either circular or linear form to saccharomyces cerevisiae or schizosaccharomyces pombe. although both yeasts could replicate the plasmid extrachromosomally, irrespective of whether it was introduced as a circular or linear structu ...19938387850
enhanced degradation of p53 protein in hpv-6 and bpv-1 e6-immortalized human mammary epithelial cells.normal mammary epithelial cells are efficiently immortalized by the e6 gene of human papillomavirus (hpv)-16, a virus commonly associated with cervical cancers. surprisingly, introduction of the e6 gene from hpv-6, which is rarely found in cervical cancer, or bovine papillomavirus (bpv)-1, into normal mammary cells resulted in the generation of immortal cell lines. the establishment of hpv-6 and bpv-1 e6-immortalized cells was less efficient and required a longer period in comparison to hpv-16 e ...19938387914
genetic definition of a new bovine papillomavirus type 1 open reading frame, e5b, that encodes a hydrophobic protein involved in altering host-cell protein processing.we have previously observed that bovine papillomavirus type 1 (bpv-1) induces the appearance of five cellular proteins in c127 mouse fibroblasts, four of which appear to arise by altered processing of resident endoplasmic reticulum proteins. studies of various cell lines revealed that expression of the 3' end of the bpv early region was sufficient for induction of these changes. to identify the bpv gene responsible, we have utilized the simian virus 40 (sv40)/bpv-1 recombinant virus pava-1, whic ...19938388507
the e1 protein of bovine papilloma virus 1 is an atp-dependent dna helicase.for efficient dna replication of papillomaviruses, only two viral-encoded proteins, e1 and e2, are required. other proteins and factors are provided by the host cell. e2 is an enhancer of both transcription and replication and is known to help e1 bind cooperatively to the origin of dna replication. e1 is sufficient for replication in extracts prepared from permissive cells, but the activity is enhanced by e2. here we show that purified e1 can act as an atp-dependent dna helicase. to measure this ...19938389467
prophylactic and therapeutic vaccination against a mucosal papillomavirus.papillomaviruses are ubiquitous dna viruses affecting humans and animals and causing a variety of tumours of mucosal and cutaneous epithelia. some of these lesions, particularly those affecting mucosal epithelia, can progress to squamous cell carcinomas. prevention or cure of viral infection would ultimately lead to a decrease in the incidence of papillomavirus-associated cancers. using recombinant proteins, we have developed prophylactic and therapeutic vaccines against bovine papillomavirus ty ...19938389809
inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene.human papillomavirus (hpv) e6 and e7 oncogenes are expressed in the great majority of human cervical carcinomas, whereas the viral e2 regulatory gene is usually disrupted in these cancers. to investigate the roles of the papillomavirus e2 genes in the development and maintenance of cervical carcinoma, the bovine papillomavirus (bpv) e2 gene was acutely introduced into cervical carcinoma cell lines by infection with high-titer stocks of simian virus 40-based recombinant viruses. expression of the ...19938389903
identification and characterization of novel promoters in the genome of human papillomavirus type 18.most studies on the regulation of gene expression in human papillomaviruses (hpv) have focused on the promoter for the early genes e6 and e7. this promoter is located at the junction between the long control region and the e6 open reading frame. rna mapping studies have suggested that additional promoters may exist in other parts of the genome. in this study, we used a combination of transcription in vitro and an analysis of rna produced in vivo in transfected cells to identify three novel promo ...19938389929
p3 promoter element of bovine papillomavirus.the p3 promoter activity of bovine papillomavirus (bpv) and cis-acting dna element of p3 promoter required for transcription were examined using chloramphenicol acetyltransferase (cat) assay. the results show that p3 promoter is a very weak promoter compared to p2 promoter in bpv and e2 transactivator is required for the maximal transcription of p3 promoter in a bpv upstream regulatory region (urr)-dependent manner. deletion experiments by nuclease bal-31 were carried out to define p3 promoter e ...19938390322
the acidic transcriptional activation domains of vp16 and p53 bind the cellular replication protein a and stimulate in vitro bpv-1 dna replication.for papillomavirus dna replication, the e2 enhancer protein cooperatively assists in binding of the e1 helicase to the origin. we report that, at limiting e1 and e2 levels, the enhancer proteins gal4-vp16 and gal4-p53(1-73) stimulate bpv in vitro dna replication. this cell-free system was used to ascertain whether the acidic activation domains have a cellular target important for replication. cellular extracts were depleted of replication activity by passage through a vp16 affinity column. the p ...19938390328
cooperative assembly of the bovine papilloma virus e1 and e2 proteins on the replication origin requires an intact e2 binding site.using quantitative gel retardation assays the properties of the bovine papilloma virus (bpv) origin recognition protein e1 and the effect of the viral e2 protein on the binding of e1 to bpv origin dna were examined. as reported previously (seo, y.s., mueller, f., lusky, m., gibbs, e., kim, h.-y., phillips, b. and j. hurwitz (1993) proc. natl. acad. sci. u. s. a. 90, 2865-2869), the e1 protein binds specifically to dna sequences within the bpv origin (ori+) of replication. we also show that the p ...19938393453
a study from south india on the association between the papilloma virus and carcinoma of the penis.specimens from 39 cases of squamous cell carcinoma of the penis were treated for the papilloma virus using the bovine papilloma virus antibody and the peroxidase-antiperoxidase technique. all 39 cases showed a viral antigen situated intranuclearly, intracytoplasmically or both intranuclearly and intracytoplasmically. no correlation could be seen between the presence of viral antigen and age of patient, duration of lesion, cell morphology and histological grade. the adjacent mucosa and skin were ...19938393502
repression of bovine papillomavirus type 1 transcription by the e1 replication protein.bovine papillomavirus type 1 (bpv-1) is the prototype virus for the study of papillomavirus gene regulation. the functions of the bpv-1 e2 proteins in transcriptional regulation have been well characterized. the bpv-1 e1 protein is required for viral dna replication and can bind to the origin of replication alone or in a complex with the e2 transactivator protein. in this study, we demonstrated that the bpv-1 e1 protein is also involved in transcriptional regulation. the e1 protein significantly ...19938394436
transformation-specific interaction of the bovine papillomavirus e5 oncoprotein with the platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor receptor cytoplasmic domain.the bovine papillomavirus e5 transforming protein appears to activate both the epidermal growth factor receptor (egf-r) and the platelet-derived growth factor receptor (pdgf-r) by a ligand-independent mechanism. to further investigate the ability of e5 to activate receptors of different classes and to determine whether this stimulation occurs through the extracellular domain required for ligand activation, we constructed chimeric genes encoding pdgf-r and egf-r by interchanging the extracellular ...19938394451
differentiation-specific expression from the bovine papillomavirus type 1 p2443 and late promoters.the papillomavirus life cycle is tightly linked with keratinocyte differentiation in squamous epithelia. vegetative viral dna replication begins in the spinous layer, while synthesis of capsid proteins and virus maturation is restricted to the most differentiated or granular layer of the epithelium. in this study, in situ hybridization of bovine fibropapillomas was used to demonstrate that the activity of two promoters of bovine papillomavirus type 1 (bpv-1) is regulated in a differentiation-spe ...19938394463
cooperative dna binding of the bovine papillomavirus e2 transcriptional activator is antagonized by truncated e2 polypeptides.cooperative dna binding of the bovine papillomavirus type 1 (bpv-1) e2 transcriptional activator (e2-ta) is thought to play a role in the transcriptional synergism of multiple e2-responsive dna elements (j. ham, n. dostatni, j.-m. gauthier, and m. yaniv, trends biochem. sci. 16:440-444, 1991). binding-equilibrium considerations show that such involvement is unlikely, thereby suggesting that the e2-ta cooperative capacity may have evolved to play other, different roles. the role of cooperative in ...19938394466
dna of bovine papillomavirus type 1 and 2 in equine sarcoids: pcr detection and direct sequencing.nucleotide sequences of bovine papillomavirus (bpv) dna amplified by the polymerase chain reaction (pcr) from samples of equine sarcoid skin tumours were determined. all naturally occurring sarcoids (n = 58 tumours from 32 horses and 2 donkeys) contained bpv-dna. all but 3 of the genome fragments belonged to the bpv type 1 strain (bpv-1); the remaining were bpv type 2. similar results were obtained with cutaneous bovine papillomas used as controls (n = 20). one of the horses, carrying 2 sarcoids ...19938394687
dna-binding domain of bovine papillomavirus type 1 e1 helicase: structural and functional aspects.the e1 protein of bovine papillomavirus type 1 is a multifunctional enzyme required for papillomaviral dna replication. it assists in the initiation of replication both as a site-specific dna-binding protein and as a dna helicase. previous work has indicated that at limiting e1 concentrations, the e2 protein is required for efficient e1 binding to the replication origin. in this study, we have defined the domain of the e1 protein required for site-specific dna binding. experiments with a series ...19938396665
importance of the bovine papillomavirus p2443 promoter in the regulation of e2 and e5 expression.the full-length bovine papillomavirus e2 gene product (e2ta), which has a direct role in dna replication and functions as a transcriptional activator, can be expressed from an unspliced mrna transcribed from the p2443 promoter or from spliced mrnas transcribed from other upstream promoters. the regulation of e2 expression from these promoters is still in question. in the background of wild-type protein coding sequences, this study identified the p2443 promoter as the major source of e2ta as well ...19938396681
human papillomavirus and cutaneous warts in meat handlers.the association of papillomavirus and hand warts in meat handlers was examined. human papillomavirus (hpv) dna was found in 23 (88%) of 26 cutaneous warts, with hpv 7 (27%) and a yet unidentified hpv (hpv x) (42%) being the predominant types. hpv 2 was found in two (7.5%) patients, and hpv 4 was found in three (11.5%) patients. no bovine papillomavirus sequences were detected. in most patients, the warts developed in less than 2 years after they started working with meat. a possible hpv transmis ...19938408588
interaction between bovine papillomavirus type 4 and cocarcinogens in the production of malignant tumours.bovine fetal palatine tissue infected with bovine papillomavirus type 4 (bpv-4) was implanted subcutaneously in athymic nude mice. the implants developed into cysts containing papillomas essentially the same as those in the natural host. in order to investigate the interaction of cocarcinogens with bpv-4 in cell transformation, the virus-infected implants were exposed in vivo to either the tumour promoter 12-o-tetradecanoylphorbol-13-acetate (tpa) or the tumour initiator 7,12-dimethylbenz[a]-ant ...19938409951
the conserved c-terminal domain of the bovine papillomavirus e5 oncoprotein can associate with an alpha-adaptin-like molecule: a possible link between growth factor receptors and viral transformation.the bovine papillomavirus e5 gene encodes an oncoprotein that can independently transform rodent fibroblasts. this small 44-amino-acid protein is thought to function through the activation of growth factor receptors. e5 activation of the epidermal growth factor receptor results in an increase in the number of activated receptors at the cell surface. this finding suggests that e5 may act by inhibiting the normal down regulation of activated epidermal growth factor receptor via coated pit-mediated ...19938413245
alanine mutagenesis of conserved residues in the platelet-derived growth factor family: identification of residues necessary for dimerization and transformation.platelet-derived growth factor (pdgf) and vascular endothelial growth factor define a family of dimeric proteins characterized by eight conserved cysteine residues involved in disulfide bonds. thirteen non-cysteine residues conserved among the platelet-derived/vascular endothelial growth factors were individually mutated to alanine in v-sis/pdgf-b. in addition, five other residues flanking f148 were also mutated to alanine. the resulting mutants were assayed for transformation of nih3t3 cells, a ...19938437840
the p12i, p13ii, and p30ii proteins encoded by human t-cell leukemia/lymphotropic virus type i open reading frames i and ii are localized in three different cellular compartments.three protein isoforms are encoded by the human t-cell leukemia/lymphotropic virus type i px region open reading frames (orf) i and ii through alternative splicing. both the singly and doubly spliced mrnas from orf i encode a single 12-kda protein (p12i), whereas two distinct proteins of 13 kda (p13ii) and 30 kda (p30ii) are encoded from the orf ii alternatively spliced mrna. because the p12i protein is very hydrophobic and poorly immunogenic, we genetically engineered its cdna by adding a short ...19938445734
1h nmr studies of the mercuric ion binding protein merp: sequential assignment, secondary structure and global fold of oxidized merp.the oxidized form of the mercuric ion binding protein merp has been studied by two-dimensional nmr. merp, which is a periplasmic water-soluble protein with 72 amino acids, is involved in the detoxification of mercuric ions in bacteria with resistance against mercury. the mercuric ions in the periplasmic space are first scavenged by the merp protein, then transported into the cytoplasm by the membrane-bound transport protein mert, and finally reduced to elementary (nontoxic) mercury by the enzyme ...19938111228
e1 protein of human papillomavirus is a dna helicase/atpase.replication of human papillomavirus (hpv) dna requires the viral proteins e1 and e2. amino acid similarities to sv40 large-t antigen had suggested that e1 is a dna helicase/atpase involved in initiating viral dna replication, and this has recently been shown for bovine papillomavirus type 1 (bpv-1) e1 protein. however, in vitro analysis of hpv e1 has been hampered by the inability to produce purified protein using heterologous expression systems. we have succeeded in demonstrating atpase and dna ...19938290339
monoclonal antibody neutralization of bpv-1.mouse monoclonal antibodies were generated against intact infectious bpv-1 virions by methods previously described (christensen et al., 1990). elisa was used to screen for reactivities to intact and/or disrupted bpv-1, crpv and hpv-11 virions. several hybridomas were initially selected that showed antibody reactivity by elisa to both intact and disrupted bpv-1, to disrupted bpv-1 only, or to intact bpv-1 virions. one monoclonal antibody, designated b1.a1, which reacted only to intact bpv-1 was s ...19937686316
the human papillomavirus type 6 and 16 e5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein.the human papillomavirus (hpv) e5 proteins are predicted from dna sequence analysis to be small hydrophobic molecules, and the hpv type 6 (hpv-6) and hpv-11 e5 proteins share several structural similarities with the bovine papillomavirus type 1 (bpv-1) e5 protein. also similar to the bpv-1 e5 protein, the hpv-6 and hpv-16 e5 proteins exhibit transforming activity when assayed on nih 3t3 and c127 cells. in this study, we expressed epitope-tagged e5 proteins from both the "low-risk" hpv-6 and the ...19937690419
retinoic acid induces loss of viral-dna, phenotypic reversion and transformation-resistance of bovine papillomavirus type-1 dna-transformed cells.two revertant cell lines were obtained by treatment of bovine papillomavirus type 1 (bpv-1) dna-transformed cell lines b3 and bf3 with 5 mum of all-trans-retinoic acid (ra) for 10 weeks. the revertant cells were devoid of detectable viral dna, no longer exhibited a transformed morphology and lost the ability to form multilayered transformed foci. they replicated with a population doubling time of 16-18 hours, which was also characteristic of the c127, b3 and bf3 cells. they attained a similar sa ...199321573367
expression of a retinoic acid-inducible mitochondrial nd5 gene is regulated by cell-density in bovine papillomavirus dna-transformed mouse c127 cells but not in revertant cells.prolonged treatment with 5 mum all-trans retinoic acid (ra) resulted in the disappearance of viral dna and phenotypic reversion in bovine papillomavirus (bpv) dna-transformed mouse c127 cells (int j oncol 3: 319-324, 1993). the ra-induced revertants exhibited increased resistance to bpv dna-induced cell transformation. using selective hybridization techniques, we have cloned a cdna sequence from an ra-induced revertant cell line, bf3ra10. sequencing data reveals that the cdna sequence was derive ...199421559589
induced regression of bovine papillomas by intralesional immunotherapy.it has long been assumed that papilloma regression is mediated by immunological mechanisms which are probably cellular in nature. the potentiation of these responses may alter the course of papilloma progression. certain strains of the bacterium corynebacterium parvum (propionibacterium acnes) have been shown to augment cellular immune mechanisms by increasing both macrophage and natural killer cell activity. this study involves the use of naturally occurring bovine papillomas to investigate the ...19947584507
vaccination against cutaneous and mucosal papillomavirus in cattle.viruses are responsible for approximately 15% of human cancer worldwide. human papillomavirus and hepatitis b virus are the recognized agents of cervical and liver cancer, respectively, which together constitute 80% of all virally induced cancers. if measures could be found to bring viral infection under control, a great proportion of human cancer would be greatly reduced. experimental vaccines are being developed against papillomavirus. in principle two different types of vaccine can be envisag ...19947796677
genomic sequences of bovine papillomaviruses in formalin-fixed sarcoids from australian horses revealed by polymerase chain reaction.seventy six formalin-fixed paraffin-embedded sarcoids from 62 australian horses, collected over a ten year period, were examined for the presence of genomic sequences from bovine papillomavirus 1 and 2 (bpv1, bpv2) with the polymerase chain reaction (pcr). sequences that could be amplified by primers specific for bpv1 and bpv2 were present in 56 of the 76 sarcoids (73%). a restriction site present in bpv1 and absent from bpv2 was detected in 28 of 34 amplified products that were treated with end ...19947801519
papillomavirus dna replication. 19947843926
transcription of papillomavirus genomes. 19947843927
transforming proteins of the papillomaviruses. 19947843928
detection, cloning and characterisation of papillomaviral dna present in sarcoid tumours of equus asinus.molecular investigations on 18 naturally occurring sarcoid tumors removed from donkeys identified papillomaviral dna homologous to bovine papillomavirus (bpv)-2 dna under stringent conditions, in all the samples. restriction endonuclease analysis of 15 of the tumours demonstrated papillomaviral dna similar to bpv-1 and bpv-2. the type of dna was not specific to either the site or the type of lesion. the analysis of the nucleotide base sequence of a cloned papillomaviral element from a sarcoid sh ...19947846835
flow cytometric quantitation of c-myc and p53 proteins in bovine papillomavirus type 1-transformed primary mouse fibroblasts.bovine papillomavirus type 1 (bpv-1)-transformed mouse fibroblast cell lines were analyzed via flow cytometry (fcm) for expression of p53 and c-myc proteins along with their dna content. in comparison to the nontransformed control cell line, significantly elevated levels of both the p53 and the c-myc protein were present in some but not all of the transformed cell lines. quantitation of p53 and c-myc proteins in cell lines containing bpv-1 dna revealed that the tumorigenic cell lines expressed h ...19947851159
[immunotherapy of tumors in agricultural domestic animals]. 19947992305
bovine cutaneous papillomas associated with bovine papillomavirus type 5.squamous papillomas obtained from bovine facial skin yielded viral dna indistinguishable from that of bovine papillomavirus type 5. it was separated from recognised bovine papillomaviruses by its restriction endonuclease pattern and hybridization tests with dna.19947998842
replication of bovine papillomavirus type 1 origin-containing dna in crude extracts and with purified proteins.the in vitro replication of dna containing the bovine papillomavirus (bpv-1) origin has been carried out with cell-free extracts from mouse fm3a and human hela cells. dna synthesis required the e1 protein, the minimal origin of replication (nucleotides 7911-22 of the bpv-1 genome), and, at low levels of fm3a extract, the addition of the human single-stranded dna-binding protein (also called rp-a or rf-a). the e2 protein was not absolutely required, but could stimulate dna synthesis at low levels ...19948006013
sequences homologous to 5' splice sites are required for the inhibitory activity of papillomavirus late 3' untranslated regions.expression of bovine papillomavirus type 1 (bpv-1) late genes is limited to terminally differentiated keratinocytes in an infected epithelium. we have previously shown that although the bpv-1 late polyadenylation site is functional in nonpermissive cells, a 53-nucleotide (nt) fragment of the late 3' untranslated region acts posttranscriptionally to reduce polyadenylated cytoplasmic rna levels. this 53-nt fragment does not appear to function by destabilizing polyadenylated cytoplasmic rna (p. a. ...19948035806
acidic transcription factors alleviate nucleosome-mediated repression of dna replication of bovine papillomavirus type 1.the papillomavirus e2 transcription factor is directly involved in viral dna replication. previous studies have shown that e2 interacts with both the viral e1 helicase and cellular replication proteins, and thus it may facilitate their targeting to the origin of replication. we demonstrate here that e1-mediated replication of bovine papillomavirus type 1 is repressed by nucleosomal assembly. the e2 protein counteracts this repression, and such activation requires the e2-binding sites adjacent to ...19948041744
[recombinant murine cell lines, transformed by various vectors based on bovine type 1 papillomavirus and expressing human tissue plasminogen activator. ii. analysis of cell lines, producing recombinant tissue plasminogen activator].we have characterized a number of recombinant cell lines established with bpv1 and lx1 (containing duplication of lcr-e6-e7 sequence) vectors on the basis of c127 cells. it had been shown that lx1 based vectors possess the higher number of intracellular copies than analogous vectors on the basis of wtbpv, and most part of them is integrated into the host genome. using various concentrations of heavy metal salts we have developed the optimized procedure for induction of recombinant tpa synthesis ...19948052253
experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle.bovine papillomavirus type 4 (bpv-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. these benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between bpv-4 and mutagenic and immunosuppressing chemicals present in the fern. the carcinomas of the upper alimentary canal are often accompanied ...19948055638
mutation of the bovine papillomavirus e5 oncoprotein at amino acid 17 generates both high- and low-transforming variants.the e5 transforming protein of bovine papillomavirus type 1 is a 44-amino-acid, hydrophobic protein which localizes predominantly to golgi membranes. the e5 transmembrane domain contains a highly conserved glutamine residue at position 17 which, from previous limited mutagenic analysis, appeared essential for transforming activity. in order to determine the specific amino acid requirements at this position, we constructed a series of substitution mutants, representing all classes of amino acids, ...19948057494
cloning and sequencing of the l1 gene of canine oral papillomavirus.canine oral papillomavirus (copv) dna was isolated from two different sources. one of these dnas was molecularly cloned and its physical map was determined. hybridization analyses using subgenomic fragments of bovine papillomavirus type 1 (bpv-1) and human papillomavirus type 16 (hpv16) as probes revealed that the cloned copv shared moderate homology within the e1 and l1 regions of bpv-1 and hpv16, whereas homology in other regions of bpv-1 and hpv16 was low. the putative l1 gene of copv was seq ...19948076829
genetically defined nuclear localization signal sequence of bovine papillomavirus e1 protein is necessary and sufficient for the nuclear localization of e1-beta-galactosidase fusion proteins.the 605 amino acid e1 protein of bovine papillomavirus type 1 (bpv-1) is a multifunctional nuclear protein required for viral dna replication. a nuclear localization signal (nls) sequence was previously defined by point mutations in three short adjacent clusters of basic amino acids located in the amino-terminal region of the e1 protein. in this study, we used a fusion protein approach to evaluate the contribution of other regions of the e1 protein to nuclear transport. the nearly full-length e1 ...19948077949
the cellular dna polymerase alpha-primase is required for papillomavirus dna replication and associates with the viral e1 helicase.persistent infection by papillomaviruses involves the maintenance of viral dna as a nuclear plasmid, the replication of which requires host dna polymerases. the role of the cellular dna polymerase alpha-primase holoenzyme was probed by using soluble extracts from rodent cells that replicate bovine papilloma virus 1 and human papilloma virus 6b dna in the presence of the viral e1 helicase and the e2 transcription factor. monoclonal antibodies directed against the catalytic 180-kda subunit of poly ...19948078945
trans activation by the full-length e2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors.papillomaviral e2 genes encode proteins that regulate viral transcription. while the full-length bovine papillomavirus type 1 (bpv-1) e2 peptide is a strong trans activator, the homologous full-length e2 product of human papillomavirus type 16 (hpv-16) appeared to vary in function in previous studies. here we show that when expressed from comparable constructs, the full-length e2 products of hpv-16 and bpv-1 trans activate a simple e2- and sp1-dependent promoter up to approximately 100-fold in h ...19948083999
role of transcriptional repressors in transformation by bovine papillomavirus type 1.transformation of rodent cells by bovine papillomavirus type 1 (bpv-1) has been shown to require the direct contribution of the viral oncogenes encoded by the e5, e6, and e7 translational open reading frames (orfs). it is also known that the viral e1 and e2 orfs contribute indirectly to cellular transformation through their transcriptional modulation of these viral oncogenes. a mutant bpv-1 disrupted in two of the proteins encoded by the e2 orf, the e2 transcriptional repressors, has a complex t ...19948084016
induction of structural changes in the bovine papillomavirus type 1 origin of replication by the viral e1 and e2 proteins.chemical and enzymatic probing techniques were used to examine the interaction of the bovine papillomavirus type 1 e1 and e2 proteins with the viral origin of replication (ori). e1 was found to generate significant distortions to the structure of ori, as assayed by kmno4 oxidation of dna. the primary site of ori distortion was located within and adjacent to the at-element of the core replicator sequence, although a number of minor structural transitions were also detected. the induction of these ...19948090734
the bovine papillomavirus e2 protein modulates the assembly of but is not stably maintained in a replication-competent multimeric e1-replication origin complex.initiation of bovine papillomavirus (bpv) dna synthesis in vivo and in vitro depends on the interaction of the viral initiator protein e1 with the replication origin (ori+ dna). the viral e2 protein assists this interaction, resulting in a cooperative assembly of both proteins on the replication origin. using gel mobility-shift experiments, we demonstrate that in the presence of both e1 and e2 proteins two classes of ori+ dna complexes were formed: complex 1 (c1) and complex 2 (c2). formation of ...19948090740
the bovine papillomavirus e1 protein alters the host cell cycle and growth properties.a stable e1-expressing cell line, ce1, was developed to investigate the effect of bovine papillomavirus e1 protein on host cell growth. expression of e1 in ce1 cells is under control of the dexamethasone-inducible mouse mammary tumor virus ltr promoter. flow cytometry was used to determine the intracellular levels of e1 in ce1 cells in parallel with cell cycle distributions and cell growth parameters. ce1 cells expressed a basal level of e1 that was increased following exposure to increasing con ...19948091648
the bovine papilloma virus e1 protein has atpase activity essential to viral dna replication and efficient transformation in cells.the bovine papilloma virus (bpv) e1 protein essential to viral dna replication has recently been shown to associate via direct protein-dna interactions with the viral origin of replication and to be an atp-dependent helicase. we show here that in accordance with the latter function, the e1 gene product has intrinsic atpase activity. mutations placed throughout the nucleotide binding consensus element abolish the atpase activity of e1 and render bpv genomes harboring such mutations defective for ...19948091670
segregation properties of bovine papillomaviral plasmid dna.essentially complete segregation of replication-competent bpv-1 plasmid dna species was observed in daughter subclones derived from primary co-transformed c127 cell lines. thus, whereas primary co-transformants retained both of two distinguishable co-transfected plasmid species, subcloning experiments revealed that morphologically transformed daughter subclones derived from such co-transformed cell lines contained only one species of viral plasmid dna. similar results were obtained with each of ...19948107134
humoral immune response to the e7 protein of bovine papillomavirus type 4 and identification of b-cell epitopes.we have previously vaccinated cattle with e7, the major transforming protein of bovine papillomavirus-4, prior to homologous virus challenge. this retarded the development of papillomas and promoted their early regression compared to control animals. to understand the mechanism for this regression, we have studied the b and t cell response in vaccinated animals and compared it to that of non-vaccinated, virus-infected animals. the b cell response is reported here. the development of e7 igg antib ...19947510442
cell-free replication of the human papillomavirus dna with homologous viral e1 and e2 proteins and human cell extracts.we have established the first homologous cell-free dna replication system for a papillomavirus. the replication of the human papillomavirus type 11 (hpv-11) origin was achieved by using human 293 cell extracts supplemented with the hpv-11 e1 and e2 proteins purified from insect cells infected with recombinant baculoviruses. efficient replication depends on the hpv-11 origin, the hpv-11 e1 and e2 proteins, as well as human dna polymerase alpha, delta, replication protein a, topoisomerase i, and t ...19947523366
neutralization of bovine papillomavirus by antibodies to l1 and l2 capsid proteins.we have generated four mouse monoclonal antibodies (mabs) to bovine papillomavirus virions that bound type-specific, adjacent, and conformationally dependent epitopes on the l1 major capsid protein. all four mabs were neutralizing at ratios of 1 mab molecule per 5 to 25 l1 molecules, but only three effectively blocked binding of the virus to the cell surface. therefore, antibodies can prevent papillomavirus infection by at least two mechanisms: inhibition of cell surface receptor binding and a s ...19947523700
cooperativity in vivo between the e2 transactivator and the tata box binding protein depends on core promoter structure.the e2 transactivator protein of bovine papillomavirus 1 (bpv-1) can strongly stimulate complex promoters such as that of the herpes simplex virus thymidine kinase gene but does not efficiently activate minimal promoters that only contain e2 binding sites and a tata box. here we show that overexpression of the human, but not yeast, tata box binding protein (tbp) in transfection experiments overcomes this block and enables e2 to activate a minimal tata box-containing promoter. this suggests that ...19948306958
papillomavirus contains cis-acting sequences that can suppress but not regulate origins of dna replication.bovine papillomavirus (bpv) dna has been reported to restrict its own replication and that of the lytic simian virus 40 (sv40) origin to one initiation event per molecule per s phase, which suggests bpv dna replication as a model for cellular chromosome replication. suppression of the sv40 origin required two cis-acting bpv sequences (ncor-1 and -2) and one trans-acting bpv protein. the results presented in this paper confirm the presence of two ncor sequences in the bpv genome that can suppress ...19948151772
the bovine papillomavirus type 1 (bpv1) replication protein e1 modulates transcriptional activation by interacting with bpv1 e2.the study of bovine papillomavirus type 1 (bpv1) dna replication has shown that e1 and e2 are the only viral proteins required for this process. both e1 and e2 interact with the viral origin of replication (ori). the bpv1 e2 protein is also a well-characterized transcriptional regulator. we show in this report that e1 can modulate transcription by interactions with e2. at low concentrations, e1 enhanced the e2-mediated transactivation of heterologous promoters containing the bpv1 ori by promotin ...19948289338
dna binding specificity of the bovine papillomavirus e1 protein is determined by sequences contained within an 18-base-pair inverted repeat element at the origin of replication.bovine papillomavirus type 1 (bpv-1) dna replicates episomally and requires two virally expressed proteins, e1 and e2, for this process. both proteins bind to the bpv-1 genome in the region that functions as the origin of replication. the binding sequences for the e2 protein have been characterized previously, but little is known about critical sequence requirements for e1 binding. using a bacterially expressed e1 fusion protein, we examined binding of the bpv-1 e1 protein to the origin region. ...19948289339
human papillomavirus type 11 e2 proteins repress the homologous e6 promoter by interfering with the binding of host transcription factors to adjacent elements.the e6 promoter of human papillomaviruses (hpvs) trophic for epithelia for the lower genital tract and the upper respiratory tract is regulated in vitro by homologous and heterologous papillomaviral e2 proteins that bind to a consensus responsive sequence (e2-rs) accn6ggt. when hpv type 11 (hpv-11) expression is examined in epithelial cell lines, the hpv-11 e2-c protein, which lacks the amino-terminal transactivating domain of the full-length e2 protein, invariably represses the homologous viral ...19948289341
characterization of the human papillomavirus e2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes.the major regulator of papillomavirus transcription is encoded by the viral e2 gene. the e2 gene has been well characterized in bovine papillomavirus (bpv) where it encodes at least three different polypeptides which differentially affect viral gene expression. in human papillomaviruses (hpvs) the e2 gene product is much less well characterized. in this study we have analysed the mechanism of action of the hpv-16, hpv-18 and bpv-1 e2 proteins in cervical keratinocytes. we show that the full leng ...19947957111
an element binding a c/ebp-related transcription factor contributes to negative regulation of the bovine papillomavirus type 4 long control region.deletion of the nr2 element of the long control region (lcr) of bovine papillomavirus type 4 (bpv-4) was observed previously to lead to a fivefold increase in enhancer activity of a subfragment of the lcr. further characterization of this element indicates that mutations in nr2 lead to increased enhancer activity in both mouse ct3 fibroblasts and in a transformed bovine epithelial cell line derived from an alimentary canal papilloma/in situ carcinoma, but not in primary bovine keratinocytes. sin ...19947964614
the genomes of the animal papillomaviruses european elk papillomavirus, deer papillomavirus, and reindeer papillomavirus contain a novel transforming gene (e9) near the early polyadenylation site.we report that the genomes of reindeer papillomavirus (rpv), european elk papillomavirus (eepv), and deer papillomavirus (dpv) contain a short conserved translational open reading frame (orf), e9, which is located between the e5 orf and the early polyadenylation site. in rpv, dpv, and eepv, e9 orfs have the potential to encode extremely hydrophobic polypeptides of approximately 40 amino acids. in mouse c127 cells transformed by eepv and rpv, there exists a unique, abundant mrna species of approx ...19947966628
replication of human papillomavirus (hpv) dnas supported by the hpv type 18 e1 and e2 proteins.transient replication of human papillomavirus (hpv) type 18 dna was shown to require the viral e1 and e2 proteins. a 108-bp sequence within the long control region (nucleotides 12 to 119) was sufficient to function as the origin, but maximal replication required a region of 177 bp from positions 7800 to 7857 and 1 to 119 of hpv-18. the e1 and e2 proteins of hpv-18 also supported transient replication of plasmids containing the origins of hpv-1a and bovine papillomavirus type 1 to low levels. int ...19948254762
a population-based seroepidemiological study of cervical cancer.the epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (hpv) type 16 or 18. we performed a seroepidemiological study of hpv and cervical cancer in the counties of västerbotten and norrbotten in northern sweden, a low-risk area for cervical cancer. sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood ...19948261434
adeno-associated virus inhibits human papillomavirus type 16: a viral interaction implicated in cervical cancer.human papillomavirus (hpv) infection, in particular that by hpv type 16, is positively associated with cervical/genital cancer. in contrast, human adeno-associated virus (aav) infection is negatively associated with these same cancers. aav has also been found to inhibit the oncogenic properties of a variety of dna viruses, including bovine papillomavirus type 1, a relative of hpv-16. taken together, these findings suggested the possibility that aav and hpv-16 might interact, with aav inhibiting ...19948174138
specific interaction between the bovine papillomavirus e5 transforming protein and the beta receptor for platelet-derived growth factor in stably transformed and acutely transfected cells.the e5 protein of bovine papillomavirus is a 44-amino-acid membrane protein which induces morphologic and tumorigenic transformation of fibroblasts. we previously showed that the e5 protein activates and forms a complex with the endogenous beta receptor for platelet-derived growth factor (pdgf) in transformed rodent fibroblasts and that the pdgf beta receptor can mediate tumorigenic transformation by the e5 protein in a heterologous cell system. other workers have identified the receptor for epi ...19948189497
latent papillomavirus infection in cattle.during a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (bpv-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either bpv-1 or bpv-2. skin warts appeared also in an immunocompetent an ...19948191003
cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus e5 oncoprotein.the e5 oncoprotein of bovine papillomavirus, only 44 amino acids long, occurs as a disulfide-bonded transmembrane dimer. this remarkable oncoprotein stimulates signal transduction through activation of the platelet-derived growth factor (pdgf) receptor, and e5 exhibits limited amino acid sequence similarity with pdgf. results presented here suggest that a key feature of the hydrophobic transmembrane domain is an amino acid side chain that participates in interhelical hydrogen bond formation. the ...19948197111
vaccination against papillomavirus in cattle. 19948205844
the bovine papillomavirus type 1 e5 transforming protein specifically binds and activates the beta-type receptor for the platelet-derived growth factor but not other related tyrosine kinase-containing receptors to induce cellular transformation.the 44-amino-acid e5 protein of bovine papillomavirus type 1 is a highly hydrophobic protein which appears to transform cells through the activation of growth factor receptors. to investigate the specificity of e5-growth factor receptor interactions required for mitogenic signaling, we utilized a nontumorigenic, murine myeloid cell line (32d) which is strictly dependent on interleukin-3 (il-3) for sustained proliferation in culture. this il-3 dependence can be functionally substituted by the exp ...19948207816
anomalous transforming behavior of a bovine papillomavirus type 1 mutant with an upstream promoter mutation.we show that the previously described high-transformation phenotype of the bovine papillomavirus type 1 mutant bpv730 is manifested only in an e6-dependent cell transformation assay. the bpv730 mutation was associated with superinduction of the putative e6 promoter, p89, after cycloheximide treatment, and with reduced activity of the p3080 promoter.19948207842
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