Publications

bovine papillomavirus transmission and chromosomal aberrations: an experimental model.	enzootic haematuria and urinary bladder cancer in cattle are associated with feeding on bracken fern and bovine papillomavirus (bpv) infection. an increased rate of chromosomal aberrations in peripheral blood lymphocytes from chronically affected haematuric cows raised in bracken fern pastures has been reported, suggesting the presence of bpv in the peripheral blood of afflicted animals. the purpose of the present investigation was to examine the role of peripheral blood as a potential bpv-trans ...	1998	9747721
role of glutamine 17 of the bovine papillomavirus e5 protein in platelet-derived growth factor beta receptor activation and cell transformation.	the bovine papillomavirus e5 protein is a small, homodimeric transmembrane protein that forms a stable complex with the cellular platelet-derived growth factor (pdgf) beta receptor through transmembrane and juxtamembrane interactions, resulting in receptor activation and cell transformation. glutamine 17 in the transmembrane domain of the 44-amino-acid e5 protein is critical for complex formation and receptor activation, and we previously proposed that glutamine 17 forms a hydrogen bond with thr ...	1998	9765437
l1-specific protection from tumor challenge elicited by hpv16 virus-like particles.	a single injection of hpv16 l1 virus-like particles induced potent cd8-mediated protection from tumor challenge by c3 cells, a line derived from embryonic mouse cells transfected with the hpv16 genome. l1 rna, but not protein, was detected biochemically in c3 cells. these results indicate that low-level expression of hpv16 l1 can occur in proliferating cells and serve as a tumor vaccine target. although l1 expression is generally thought to be restricted to terminally differentiated epithelial c ...	1998	9792847
a pyrimidine-rich exonic splicing suppressor binds multiple rna splicing factors and inhibits spliceosome assembly.	the bovine papillomavirus type 1 (bpv-1) exonic splicing suppressor (ess) is juxtaposed immediately downstream of bpv-1 splicing enhancer 1 and negatively modulates selection of a suboptimal 3' splice site at nucleotide 3225. the present study demonstrates that this pyrimidine-rich ess inhibits utilization of upstream 3' splice sites by blocking early steps in spliceosome assembly. analysis of the proteins that bind to the ess showed that the u-rich 5' region binds u2af65 and polypyrimidine trac ...	1998	9826658
recruitment and loading of the e1 initiator protein: an atp-dependent process catalysed by a transcription factor.	initiation of dna replication critically depends on ori recognition as well as on catalytic activities of the initiator complex. for replication of papillomaviruses the catalytic activities for initiation are provided by the e1 protein. here, we show that the transcription factor e2 acts to assemble e1 into a complex active for ori distortion in two steps. first, cooperative dna binding of e1 and e2 generates a sequence-specific ori recognition complex. in the second atp-dependent step, e2 is di ...	1998	9843509
function of a bovine papillomavirus type 1 exonic splicing suppressor requires a suboptimal upstream 3' splice site.	alternative splicing is an important mechanism for the regulation of bovine papillomavirus type 1 (bpv-1) gene expression during the virus life cycle. previous studies in our laboratory have identified two purine-rich exonic splicing enhancers (eses), se1 and se2, located between two alternative 3' splice sites at nucleotide (nt) 3225 and nt 3605. further analysis of bpv-1 late-pre-mrna splicing in vitro revealed a 48-nt pyrimidine-rich region immediately downstream of se1 that inhibits utilizat ...	1999	9847303
structural models of the bovine papillomavirus e5 protein.	the bovine papillomavirus e5 protein is thought to be a type ii integral membrane protein that exists as a disulfide-linked homodimer in transformed cells. polarized-infrared measurements show that the e5 dimer in membrane bilayers is largely alpha-helical and has a transmembrane orientation. computational searches of helix-helix conformations reveal two possible low-energy dimer structures. correlation of these results with previous mutagenesis studies on the e5 protein suggests how the e5 dime ...	1998	9849943
dna curvature and deformation in protein-dna complexes: a step in the right direction.		1998	9860938
structural code for dna recognition revealed in crystal structures of papillomavirus e2-dna targets.	transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein e2 to several sites in the viral genome. crystal structures of bovine papillomavirus e2 dna targets reveal a conformational variant of b-dna characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. a comparison between the free and the protein-bound dna demonstrates that the intrinsic structure of the dna regions contacted directly by the protein and the deformabili ...	1998	9860945
bovine papillomavirus e5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor beta receptor.	the bovine papillomavirus e5 protein is a 44-aa transmembrane protein that forms a stable complex with the cellular platelet-derived growth factor (pdgf) beta receptor and induces constitutive tyrosine phosphorylation and activation of the receptor, resulting in cell transformation. the e5 protein does not resemble pdgf, but rather activates the receptor in a ligand-independent fashion, thus providing a unique system to examine activation of receptor tyrosine kinases. here, we used a variety of ...	1998	9860953
mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice.	it has been shown previously that recombinant virus-like particles (vlps) of papillomavirus can induce vlp-specific humoral and cellular immune responses following parenteral administration. to test whether mucosal administration of bovine papillomavirus type 1 (bpv1) vlps could produce mucosal as well as systemic immune responses to vlps, 50 micrograms chimeric bpv1 vlps containing an hpv16 e7 ctl epitope (bpvl1/e7 vlp) was administered intranasally to mice. after two immunisations, l1-specific ...	1998	9875315
crystal structure of the e2 dna-binding domain from human papillomavirus type 16: implications for its dna binding-site selection mechanism.	the crystal structure of the e2 dna-binding domain from the high-risk cervical cancer-associated strain human papillomavirus type 16 (hpv-16) is described here. the papillomavirus e2 proteins regulate transcription from all viral promoters and are required for the initiation of replication in vivo. they belong to a family of viral proteins that form dimeric beta-barrels and use surface alpha-helices for dna interaction. although all e2 proteins recognize the same consensus, palindromic dna seque ...	1998	9878365
human papillomavirus dna replication compartments in a transient dna replication system.	many dna viruses replicate their genomes at nuclear foci in infected cells. using indirect immunofluorescence in combination with fluorescence in situ hybridization, we colocalized the human papillomavirus (hpv) replicating proteins e1 and e2 and the replicating origin-containing plasmid to nuclear foci in transiently transfected cells. the host replication protein a (rp-a) was also colocalized to these foci. these nuclear structures were identified as active sites of viral dna synthesis by brom ...	1999	9882301
virocrine transformation: the intersection between viral transforming proteins and cellular signal transduction pathways.	this review describes a mechanism of viral transformation involving activation of cellular signaling pathways. we focus on four viral oncoproteins: the e5 protein of bovine papillomavirus, which activates the platelet-derived growth factor beta receptor; gp55 of spleen focus forming virus, which activates the erythropoietin receptor; polyoma virus middle t antigen, which resembles an activated receptor tyrosine kinase; and lmp-1 of epstein-barr virus, which mimics an activated tumor necrosis fac ...	1998	9891803
a broad-spectrum microbicide with virucidal activity against sexually transmitted viruses.	sodium dodecyl sulfate (sds), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. in preliminary experiments, we demonstrated that sds is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. we hypothesized that sds might be capable of denaturing the capsid proteins of nonenve ...	1999	9925525
biochemical and electron microscopic image analysis of the hexameric e1 helicase.	dna replication initiator proteins bind site specifically to origin sites and in most cases participate in the early steps of unwinding the duplex. the papillomavirus preinitiation complex that assembles on the origin of replication is composed of proteins e1 and the activator protein e2. e2 is an ancillary factor that increases the affinity of e1 for the ori site through cooperative binding. here we show that duplex dna affects e1 (in the absence of e2) to assemble into an active hexameric stru ...	1999	9933649
the bovine papillomavirus type 4 long control region contains an epithelial specific enhancer.	bovine papillomavirus type 4 (bpv-4) is a mucosal epitheliotropic virus that is a causative agent in alimentary carcinoma of cattle. the long control region (lcr) of this virus controls expression of the transforming proteins, e8 and e7. deletion mutants of the lcr were prepared and assayed for their ability to activate transcription from the lcr promoter in primary bovine palate keratinocytes (the natural target cell for bpv-4) and fibroblasts. the lcr was at least an order of magnitude more ac ...	1999	9934679
the bovine papillomavirus type 1 e6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.	expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of tumor necrosis factor alpha (tnf). while murine c127 cells containing the bovine papillomavirus type 1 (bpv-1) genome were reported to exhibit increased tnf sensitivity, the gene(s) responsible was not identified. the bpv-1 e6 oncoprotein induces tumorigenic transformation of murine c127 cells and stimulates transcription when targeted to a promoter. bpv-1 e6 was introduced into c127 cells (pbe6) by ret ...	1999	9989810
detection of human papillomavirus type 10 dna in eccrine syringofibroadenomatosis occurring in clouston's syndrome.	syringofibroadenomatosis is often associated with an underlying condition such as diabetes mellitus or hidrotic ectodermal dysplasia. by reason of these associations, a reactive or hamartomatous cause is suspected. we report a case of a 71-year-old woman with clouston's syndrome in whom progressive multiple palmoplantar syringofibroadenomas developed over a 10-year period. the syringofibroadenomas formed flat-topped papules simulating verruca plana; the widespread distribution and chronic progre ...	1999	10025758
characteristics of cytosine deaminase-5-fluorocytosine system. enhancement of radiation cytotoxicity and bystander effect.		1998	10026860
induction of autoantibodies to mouse ccr5 with recombinant papillomavirus particles.	the vertebrate immune system has evolved to respond vigorously to microbial infection but to ignore self-antigens. evidence has emerged that b cell responses to viruses are initiated by immune recognition of ordered arrays of antigen on the viral surface. to test whether autoantibodies against a self-antigen can be induced by placing it in a context that mimics the ordered surface of a viral particle, a peptide representing an extracellular loop of the mouse chemokine receptor ccr5 was incorpora ...	1999	10051649
a mutational analysis of the transforming functions of the e8 protein of bovine papillomavirus type 4.	the e8 protein of bpv-4 contributes to transformation of primary bovine cells (palfs) by inducing anchorage-independent growth and by down-regulating gap junction intercellular communication, likely due to its binding to 16k ductin. we show here that, in addition, e8 confers on palf cells the ability to grow in low serum and to escape from contact inhibition (focus formation). e8 also transactivates an exogenous human cyclin a gene promoter, suggesting that overexpression of cyclin a is responsi ...	1999	10069964
the bovine papillomavirus e5 protein requires a juxtamembrane negative charge for activation of the platelet-derived growth factor beta receptor and transformation of c127 cells.	the bovine papillomavirus e5 gene encodes a 44-amino-acid, homodimeric transmembrane protein that is the smallest known transforming protein. the e5 protein transforms cultured fibroblasts by forming a stable complex with the endogenous platelet-derived growth factor (pdgf) beta receptor through transmembrane and juxtamembrane interactions, leading to sustained receptor activation. aspartic acid 33 in the extracellular juxtamembrane region of the e5 protein is important for cell transformation a ...	1999	10074180
structure of the e2 dna-binding domain from human papillomavirus serotype 31 at 2.4 a.	the papillomaviruses are a family of small double-stranded dna viruses which exclusively infect epithelial cells and stimulate the proliferation of those cells. a key protein within the papillomavirus life-cycle is known as the e2 (early 2) protein and is responsible for regulating viral transcription from all viral promoters as well as for replication of the papillomavirus genome in tandem with another protein known as e1. the e2 protein itself consists of three functional domains: an n-termina ...	1998	10089498
molecular replacement: the revival of the molecular fourier transform method.	the molecular fourier transform method, perhaps the first application of the molecular-replacement approach, used in the 1950s for the two-dimensional structure determination of small molecules, has been modernised for the efficient solution of complex structures. in the modern application of the molecular fourier transform (mft), the three-dimensional transform of the molecular model is calculated and fitting is achieved by rotating the weighted reciprocal lattice with respect to the calculated ...	1998	10089509
the transmembrane domain of the e5 oncoprotein contains functionally discrete helical faces.	the e5 protein of bovine papillomavirus is a 44-amino acid, golgi-resident, type ii transmembrane protein that efficiently transforms immortalized mouse fibroblasts. the transmembrane (tm) domain of e5 is not only critical for biological activity, it also regulates interactions with cellular targets including the platelet derived growth factor receptor (pdgf-r) and the 16-kda subunit of the vacuolar proton atpase (v-atpase). in order to define the specific tm amino acids essential for e5 biologi ...	1999	10187811
long-term episomal maintenance of bovine papillomavirus type 1 plasmids is determined by attachment to host chromosomes, which is mediated by the viral e2 protein and its binding sites.	papillomavirus genomes are stably maintained as extrachromosomal nuclear plasmids in dividing host cells. to address the mechanisms responsible for stable maintenance of virus, we examined nuclear compartmentalization of plasmids containing the full-length upstream regulatory region (urr) from the bovine papillomavirus type 1 (bpv1) genome. we found that these plasmids are tightly associated with the nuclear chromatin both in the stable cell lines that maintain episomal copies of the plasmids an ...	1999	10196338
persistent expression of foreign genes in cultured hepatocytes: expression vectors.	we have optimized a liposome-based transfection method that mediated highly efficient stable expression of foreign genes in hepatocytes. moreover, we have observed that the metallothionein 1 promoter in the bovine papilloma virus-based expression vector drove the highest expression of foreign genes in hepatocytes as compared with the cytomegalovirus and the human polypeptide chain elongation factor 1alpha (ef-1alpha) promoters in the pcdna 3-based expression vector. the cytomegalovirus promoter ...	1999	10196472
effect of bovine papillomavirus e2 protein-specific monoclonal antibodies on papillomavirus dna replication.	the bovine papillomavirus type 1 (bpv-1) e2 protein is the master regulator of papillomavirus replication and transcription. we have raised a panel of monoclonal antibodies (mabs) against the bpv-1 e2 protein and used them to probe the structure and function of the protein. five mabs reacted with linear epitopes, and four mabs recognized conformation-dependent epitopes which mapped within the c-terminal dna-binding and dimerization domain. mab 1e2 was able to recognize the replication- and trans ...	1999	10233926
interactions of the papovavirus dna replication initiator proteins, bovine papillomavirus type 1 e1 and simian virus 40 large t antigen, with human replication protein a.	papovaviruses utilize predominantly cellular dna replication proteins to replicate their own viral genomes. to appropriate the cellular dna replication machinery, simian virus 40 (sv40) large t antigen (tag) binds to three different cellular replication proteins, the dna polymerase alpha-primase complex, the replication protein a (rpa) complex, and topoisomerase i. the functionally similar papillomavirus e1 protein has also been shown to bind to the dna polymerase alpha-primase complex. enzyme-l ...	1999	10233951
papillomavirus capsid protein expression level depends on the match between codon usage and trna availability.	translation of mrna encoding the l1 and l2 capsid proteins of papillomavirus (pv) is restricted in vivo to differentiated epithelial cells, although transcription of the l1 and l2 late genes occurs more widely. the codon composition of pv late genes is quite different from that of most mammalian genes. to test the possibility that pv late gene codon composition determines the efficiency of pv late gene expression in some cell types, synthetic bovine papillomavirus type 1 (bpv1) late genes were c ...	1999	10233959
role of the atp-binding domain of the human papillomavirus type 11 e1 helicase in e2-dependent binding to the origin.	replication of the genome of human papillomaviruses (hpv) is initiated by the recruitment of the viral e1 helicase to the origin of dna replication by the viral e2 protein, which binds specifically to the origin. we determined, for hpv type 11 (hpv-11), that the c-terminal 296 amino acids of e1 are sufficient for interaction with the transactivation domain of e2 in the yeast two-hybrid system and in vitro. this region of e1 encompasses the atp-binding domain. here we have examined the role of th ...	1999	10364274
nucleotides 1506-1625 of bovine papillomavirus type 1 genome can enhance dna packaging by l1/l2 capsids.	we have previously described a dna-packaging assay using bovine papillomavirus type 1 (bpv-1) virus-like particles (vlps) and have identified a region of the bpv genome that assists in packaging. in this study, we identify a specific bpv sequence involved in dna packaging by bpv-1 vlps. in the initial screening of bpv-1 genomic sequences essential for dna packaging, we observed that a plasmid with deletions between nucleotides (nt) 948 and 2113 failed to be packaged into bpv-1 vlps. however, pla ...	1999	10364505
high precision solution structure of the c-terminal kh domain of heterogeneous nuclear ribonucleoprotein k, a c-myc transcription factor.	among it's many reported functions, heterogeneous nuclear ribonucleoprotein (hnrnp) k is a transcription factor for the c- myc gene, a proto-oncogene critical for the regulation of cell growth and differentiation. we have determined the solution structure of the gly26-->arg mutant of the c-terminal k-homology (kh) domain of hnrnp k by nmr spectroscopy. this is the first structure investigation of hnrnp k. backbone residual dipolar couplings, which provide information that is fundamentally differ ...	1999	10369774
identification of survival motor neuron as a transcriptional activator-binding protein.	spinal muscular atrophy (sma) is an inherited neuro-muscular disease characterized by specific degeneration of spinal cord anterior horn cells and subsequent muscle atrophy. survival motor neuron ( smn ), located on chromosome 5q13, is the sma-determining gene. in the nucleus, smn is present in large foci called gems, the function of which is not yet known, while cytoplasmic smn has been implicated in snrnp biogenesis. in sma patients, smn protein levels and the number of gems generally correlat ...	1999	10369867
bovine papillomavirus e2 protein activates a complex growth-inhibitory program in p53-negative ht-3 cervical carcinoma cells that includes repression of cyclin a and cdc25a phosphatase genes and accumulation of hypophosphorylated retinoblastoma protein.	the bovine papillomavirus e2 protein can inhibit the proliferation of ht-3 cells, a p53-negative cervical carcinoma cell line containing integrated human papillomavirus type 30 dna. here, we analyzed ht-3 cells to explore the mechanism of p53-independent e2-mediated growth inhibition. expression of the e2 protein repressed expression of the endogenous human papillomavirus type 30 e6/e7 genes. this was accompanied by hypophosphorylation and increased accumulation of p105rb and repression of e2f1 ...	1999	10392903
nucleotide sequence and characterization of human papillomavirus type 83, a novel genital papillomavirus.	studies of human papillomaviruses (hpv) are hampered by the lack of a conventional culture system, because hpv completes its life cycle only in fully differentiated human tissue. to overcome this obstacle, the athymic mouse xenograft system has been used to study the pathogenesis of a limited number of hpv types. we recently reported the propagation of a novel hpv type in the mouse xenograft system and the cloning of its genome. consensus primer pcr had previously identified this virus as mm7, l ...	1999	10405368
many different papillomaviruses have low transcriptional activity in spite of strong epithelial specific enhancers.	transcription of the e6-e7 genes of human papillomavirus type 11 (hpv-11), hpv-16 and hpv-18 is specific to epithelial cells. this mechanism originates from synergism between different transcription factors such as ap-1, nfi and sp1, which occur in many different cell types, but whose activity is biased in favour of epithelial cells. in this study, the transcriptional regulation of 14 different papillomavirus types in the absence of the viral e2 transcription factor was compared. genital hpv typ ...	1999	10423140
papillomavirus e2 induces p53-independent apoptosis in hela cells.	we have previously shown that expression of the papillomavirus e2 protein in hela cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. in contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. in the present study, we conducted biochemical and genetic experiments in order to determine whether e2-induced apoptosis was independent of p53 induction. we showed that e2 did not alter the transcription of bax, a know ...	1999	10467398
bovine papillomaviral gene expression in equine sarcoid tumours.	the sarcoid is a benign locally invasive dermal fibroblastic lesion, commonly affecting horses and donkeys. the aetiology of the equine sarcoid is equivocal. bovine papillomaviral (bpv) dna (type 1/2) is frequently demonstrable in equine sarcoid tumour biopsies. however, the exact role of the virus in the disease process and its contribution to the phenotypic differences in sarcoids is not known. it was sought to assess the transcriptional activity of bpv-1 found in sarcoid tissues. of 20 tumour ...	1999	10475087
an enhanced epithelial response of a papillomavirus promoter to transcriptional activators.	mucosal epitheliotropic papillomaviruses have a similar long control region (lcr) organization: a promoter region, an enhancer region, and a highly conserved distribution of e2 dna binding sites. the enhancer of these viruses is epithelial-specific, as it fails to activate transcription from heterologous promoters in nonepithelial cell types (gloss, b., bernard, h. u., seedorf, k., and klock, g. (1987) embo j. 6, 3735-3743; morgan, i. m., grindlay, g. j., and campo, m. s. (1999) j. gen. virol. 8 ...	1999	10488130
binding of the human papillomavirus type 16 p97 promoter by the adeno-associated virus rep78 major regulatory protein correlates with inhibition.	human papillomavirus type 16 (hpv-16) infection is positively associated with cervical cancer, whereas adeno-associated virus (aav) infection is negatively associated with this same cancer. in earlier studies these two virus types have been shown to directly interact, with aav inhibiting or enhancing papillomavirus functions depending upon the specific circumstances. one defined interaction between these two viruses is the ability of the aav rep78 major regulatory protein to inhibit gene express ...	1999	10531369
mutation correction by homologous recombination with an adenovirus vector.		2000	10561834
protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation.	while it has been known for more than 20 years that unusually stable cysteine-sulfenic acid (cys-soh) derivatives can be introduced in selected proteins by mild oxidation, only recently have chemical and crystallographic evidence for functional cys-soh been presented with native proteins such as nadh peroxidase and nadh oxidase, nitrile hydratase, and the horf6 and ahpc peroxiredoxins. in addition, cys-soh forms of protein tyrosine phosphatases and glutathione reductase have been suggested to pl ...	1999	10569923
two distinct regions of the bpv1 e1 replication protein interact with the activation domain of e2.	papillomavirus e1 and e2 proteins co-operation in viral dna replication is mediated by protein-protein interactions that lead to formation of an e1-e2 complex. to identify the domains involved, portions of the two proteins were expressed as fusions to the dna-binding protein lexa or the transactivation domain of vp16 and analyzed by the yeast two-hybrid system. the c-terminal 266 amino acids of bpv1 e1 (e1c266) interacted strongly with e2 in the yeast system and in a mammalian two-hybrid assay. ...	1999	10581387
structural correlates for enhanced stability in the e2 dna-binding domain from bovine papillomavirus.	papillomaviral e2 proteins participate in viral dna replication and transcriptional regulation. we have solved the solution structure of the dna-binding domain of the e2 protein from bovine papillomavirus (bpv-1). the structure calculation used 2222 distance and 158 dihedral angle restraints for the homodimer (202 residues in total), which were derived from homonuclear and heteronuclear multidimensional nuclear magnetic resonance (nmr) spectroscopic data. the root-mean-square deviation for struc ...	1999	10587434
identification of a short, hydrophilic amino acid sequence critical for origin recognition by the bovine papillomavirus e1 protein.	the e1 protein of bovine papillomavirus (bpv) is a site-specific dna binding protein that recognizes an 18-bp inverted repeat element in the viral origin of replication. sequence-specific dna binding function maps to the region from approximately amino acids 140 to 300, and isolated polypeptides containing this region have been shown to retain origin binding in vitro. to investigate the sequence and structural characteristics which contribute to sequence-specific binding, the primary sequence of ...	2000	10590112
the differentiation-specific factor cdp/cut represses transcription and replication of human papillomaviruses through a conserved silencing element.	the life cycles of human papillomaviruses (hpvs) are intimately linked to the differentiation program of infected stratified epithelia, with both viral gene expression and replication being maintained at low levels in undifferentiated basal cells and increased upon host cell differentiation. we recently identified, in hpv-16, a negative regulatory element between the epithelial-cell-specific enhancer and the e6 promoter that is capable of silencing e6 promoter activity, and we termed this elemen ...	2000	10590129
a method for efficient extraction of bovine papilloma virus-based minichromosomes that preserves native chromatin structure.	aiming to create an adequate model for investigation of the molecular mechanisms involved in transcriptional regulation by steroid hormones, a number of cell lines carrying bovine papilloma virus (bpv) based constructs containing the mouse mammary tumor virus long terminal repeat (ltr) were established (ostrowski et al., mol. cell. biol. 3, 2945-2957, 1983). however, all our attempts to extract from the cells such minichromosomes as nucleoprotein complexes using a method previously described (os ...	1999	10619601
identification of a second transforming function in bovine papillomavirus type 1 e6 and the role of e6 interactions with paxillin, e6bp, and e6ap.	papillomavirus e6 oncoproteins transform mammalian cells through interaction with cellular proteins. bovine papillomavirus type 1 e6 (be6) interacts with three previously described cellular targets: the e6ap e3 ubiquitin ligase, the calcium-binding protein e6bp (also known as erc-55), and paxillin, which is a focal adhesion adapter protein. be6 interacts strongly with each of these proteins in vitro, binding to similar peptide sequences found in e6ap, e6bp, and paxillin. to determine which be6 i ...	2000	10623743
two patches of amino acids on the e2 dna binding domain define the surface for interaction with e1.	the e1 and e2 proteins from bovine papillomavirus bind cooperatively to the viral origin of dna replication (ori), forming a complex which is essential for initiation of dna replication. cooperative binding has two components, in which (i) the dna binding domains (dbds) of the two proteins interact with each other and (ii) the e2 transactivation domain interacts with the helicase domain of e1. by generating specific point mutations in the dbd of e2, we have defined two patches of amino acids tha ...	2000	10627562
adeno-associated virus rep78 binds to e2-responsive element 1 of bovine papillomavirus type 1.	adeno-associated virus type-2 (aav-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transformation of bovine papillomavirus type-1 (bpv-1) and other transforming dna viruses. previous studies have suggested that the rep78 protein of aav-2 is a key player mediating this effect. in this report we have analyzed the effect of aav-2 rep78 protein on the regulation of gene expression of a reporter gene under the control of the long control reg ...	1999	10632568
stable maintenance of linear bovine papillomavirus 1 molecules in c127i cells.	this paper describes the characterization of cell lines that stably maintain linear copies of bovine papillomavirus 1 (bpv-1). cell lines were generated by liposome-mediated transfection of bamh1-linearized virus into c127i cells. two transfectants with morphologies differing from each other and from that of the parental cell line were characterized. southern blots indicated that they contain ten to twelve copies of the bpv-1 genome per cell and that the predominant species in both cell lines ar ...	1999	10643966
feline papillomas and papillomaviruses.	papillomaviruses (pvs) are highly species- and site-specific pathogens of stratified squamous epithelium. although pv infections in the various felidae are rarely reported, we identified productive infections in six cat species. pv-induced proliferative skin or mucous membrane lesions were confirmed by immunohistochemical screening for papillomavirus-specific capsid antigens. seven monoclonal antibodies, each of which reacts with an immunodominant antigenic determinant of the bovine papillomavir ...	2000	10643975
alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4.	recently, alpha6 integrin has been proposed as the epithelial cell receptor for papillomavirus. this study investigated whether alpha6 integrin is the cellular receptor for bovine papillomavirus type 4 (bpv-4), which is strictly epitheliotropic and infects the mucous epithelium of the upper digestive tract. primary bovine mucosal keratinocytes from the palate of a foetus (palk) displayed high levels of alpha6 integrin; matched primary fibroblasts from the same biopsy (palf) expressed almost no a ...	2000	10644830
golgi alkalinization by the papillomavirus e5 oncoprotein.	the e5 oncoprotein of bovine papillomavirus type i is a small, hydrophobic polypeptide localized predominantly in the golgi complex. e5-mediated transformation is often associated with activation of the pdgf receptor (pdgf-r). however, some e5 mutants fail to induce pdgf-r phosphorylation yet retain transforming activity, suggesting an additional mechanism of action. since e5 also interacts with the 16-kd pore-forming subunit of the vacuolar h(+)-atpase (v-atpase), the oncoprotein could conceiva ...	2000	10648563
a structural model for the rola protein and its interaction with dna.	the study of the plant oncogene rola has been hampered by a lack of structural information. here we show that, despite a lack of significant sequence similarity to proteins of known structure, the rola sequence adopts a known fold; that of the papillomavirus e2 dna-binding domain. this fold is reliably identified by modern threading programs, which consider predicted secondary structure, but not by others. although the rola sequence is only around 16% identical to those of the available template ...	1999	10651283
transcription factor-dependent loading of the e1 initiator reveals modular assembly of the papillomavirus origin melting complex.	replication of bovine papillomavirus type 1 dna absolutely requires the viral transcription factor e2 as well as the initiator e1, although e1 alone has all the activities expected of an initiator protein. e1 assembles on the dna in a stepwise fashion and undergoes a transition in activities from site-specific dna-binding protein to mobile helicase. complex assembly is assisted by the viral transcription factor e2 at two levels. e2 acts generally as a specificity factor, which through cooperativ ...	2000	10652347
inhibition of the bovine papillomavirus e2 protein activity by peptide nucleic acid.	the bovine papillomavirus type-1 e2 protein is the master regulator of the papillomavirus transcription and replication, the activity of which is regulated through sequence-specific dna binding. peptide nucleic acid (pna) is a nucleic acid analogue, which associates with high affinity to complementary dna, rna or pna, yielding in formation of stable complexes. the potential use of pna as a sequence-specific inhibitor of the e2 protein activity is studied in this report. we demonstrate that repla ...	2000	10653916
e5 oncoprotein mutants activate phosphoinositide 3-kinase independently of platelet-derived growth factor receptor activation.	the e5 oncoprotein of bovine papillomavirus type 1 is a golgi-resident, 44-amino acid polypeptide that can transform fibroblast cell lines by activating endogenous platelet-derived growth factor receptor beta (pdgf-r). however, the recent discovery of e5 mutants that exhibit strong transforming activity but minimal pdgf-r tyrosine phosphorylation indicates that e5 can potentially use additional signal transduction pathway(s) to transform cells. we now show that two classes of e5 mutants, despite ...	2000	10671555
binding of bovine papillomavirus type 4 e8 to ductin (16k proteolipid), down-regulation of gap junction intercellular communication and full cell transformation are independent events.	the e8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide that contributes to primary cell transformation by conferring to cells the ability to form foci and to grow in low serum and in suspension. wild-type e8 binds in vitro to ductin, a component of gap junctions, and this binding is accompanied by a loss of gap junction intercellular communication in transformed bovine fibroblasts. however, through the analysis of a panel of e8 mutants, we show here tha ...	2000	10675405
repression of the integrated papillomavirus e6/e7 promoter is required for growth suppression of cervical cancer cells.	the human papillomavirus (hpv) e2 protein is an important regulator of viral e6 and e7 gene expression. e2 can repress the viral promoter for e6 and e7 expression as well as block progression of the cell cycle in cancer cells harboring the dna of "high-risk" hpv types. although the phenomenon of e2-mediated growth arrest of hela cells and other hpv-positive cancer cells has been well documented, the specific mechanism by which e2 affects cellular proliferation has not yet been elucidated. here, ...	2000	10684283
position-dependent inhibition of the cleavage step of pre-mrna 3'-end processing by u1 snrnp.	the 3' ends of most eukaryotic pre-mrnas are generated by 3' endonucleolytic cleavage and subsequent polyadenylation. 3'-end formation can be influenced positively or negatively by various factors. in particular, u1 snrnp acts as an inhibitor when bound to a 5' splice site located either upstream of the 3'-end formation signals of bovine papilloma virus (bpv) late transcripts or downstream of the 3'-end processing signals in the 5' ltr of the hiv-1 provirus. previous work showed that in bpv it i ...	2000	10688357
parameters that affect in vitro splicing of bovine papillomavirus type 1 late pre-mrnas.	during the course of study on regulated viral pre-mrna splicing, an in vitro rna splicing assay was developed to analyze how an exonic splicing enhancer stimulates splicing of bovine papillomavirus type 1 (bpv-1) late pre-mrnas. the optimal concentration of hela nuclear extract (hne) in a standard rna splicing reaction depends on the individual substrate pre-mrna. splicing of a bpv-1 late pre-mrna required 40% hne and 2 h incubation at 30 degrees c. higher hne was detrimental to splicing and lon ...	2000	10716353
monitoring and purification of proteins using bovine papillomavirus e2 epitope tags.	we describe here the use of two newly mapped bovine papillomavirus type 1 (bpv-1) e2 protein epitopes as tags. we constructed several vector plasmids for overexpression as well as for moderate expression of single- or double-tagged proteins in either escherichia coli or eukaryotic cells. the new tags were fused to several proteins, and the activity of the tagged proteins was tested in different assays. the tags were shown not to interfere with the function of these proteins in vivo and in vitro. ...	2000	10723557
bovine papillomavirus e5 protein induces the formation of signal transduction complexes containing dimeric activated platelet-derived growth factor beta receptor and associated signaling proteins.	the bovine papillomavirus e5 protein binds to the cellular platelet-derived growth factor (pdgf) beta receptor, resulting in constitutive activation of the receptor and cell growth transformation. by subjecting extracts from e5-transformed or pdgf-treated cells to velocity sedimentation in sucrose gradients, activated pdgf beta receptor complexes were separated from monomeric, inactive receptor. rapidly sedimenting activated complexes contained oligomeric (apparently dimeric), tyrosine-phosphory ...	2000	10734138
human tumor growth is inhibited by a vaccinia virus carrying the e2 gene of bovine papillomavirus.	papillomavirus is the etiologic agent associated with cervical carcinoma. the papilloma e2 protein is able to regulate negatively the expression of e6 and e7 papilloma oncoproteins. therefore, a new, highly attenuated vaccinia virus known as modified vaccinia virus ankara (mva), which carries the papillomavirus e2 gene, was used for the treatment of tumors associated with human papillomavirus.	2000	10738224
cloning and characterization of a novel caprine genomic repetitive element that hybridizes with papillomavirus dna.	a goat genomic library was screened by southern blot hybridization at reduced stringency with a bovine papillomavirus type 5 (bpv 5) dna probe in order to identify potential cellular and viral sequences related to the papillomavirus genome. a recombinant clone with an 8.5 kb genomic insert was found to contain a 1.3 kb psti subfragment (designated as p1-1) that hybridized with the dna of bpv 5, two murine papillomaviruses and human papillomavirus types 5 and 8, but not with dna from another eigh ...	2000	10768774
interaction of the papillomavirus e2 protein with mitotic chromosomes.	the bovine papillomavirus e2 transactivator protein is a multifunctional protein that activates viral transcription, cooperates in initiation of viral dna replication, and is required for long-term episomal maintenance of viral genomes. we have shown previously that the e2 transactivator protein and bovine papillomavirus type 1 genomes are associated with mitotic chromosomes and have proposed that e2 links the genomes to cellular chromosomes to ensure segregation to daughter nuclei. in this stud ...	2000	10772985
cell-specific modulation of papovavirus replication by tumor suppressor protein p53.	small dna tumor viruses like human papillomaviruses, simian virus 40, and adenoviruses modulate the activity of cellular tumor suppressor proteins p53 and/or prb. these viruses replicate as nuclear multicopy extrachromosomal elements during the s phase of the cell cycle, and it has been suggested that inactivation of p53 and prb is necessary for directing the cells to the s phase. mouse polyomavirus (py), however, modulates only the prb protein activity without any obvious interference with the ...	2000	10775606
the bovine papillomavirus e2 transactivator is stimulated by the e1 initiator through the e2 activation domain.	bovine papillomavirus type 1 (bpv-1) encodes two regulatory proteins, e1 and e2, that are essential for viral replication and transcription. e1, an atp-dependent helicase, binds to the viral ori and is essential for viral replication, while the viral transcriptional activator, e2, plays cis-dominant roles in both viral replication and transcription. at low reporter concentrations, e1 stimulates e2 enhancer function, while at high reporter concentrations, repression results. an analysis of cis re ...	2000	10793002
production of infectious bovine papillomavirus from cloned viral dna by using an organotypic raft/xenograft technique.	bovine papillomavirus type 1 (bpv-1) induces fibropapillomas in its natural host and can transform fibroblasts in culture. the viral genome is maintained as an episome within fibroblasts, which has allowed extensive genetic analyses of the viral functions required for dna replication, gene expression, and transformation. much less is known about bpv-1 gene expression and replication in bovine epithelial cells because the study of the complete viral life cycle requires an experimental system capa ...	2000	10805809
expression vector with dna of bovine papilloma virus 1 for keratinocyte gene therapy.	although there are several methods for introducing the genes to keratinocytes in vivo, expression of transgene does not last long enough for effective keratinocyte gene therapy. in this study, we added bovine papilloma virus 1 (bpv) dna into expression vectors with the lacz gene driven by metallothionein and keratin 10 promoters, and we transferred them into keratinocytes in vivo using the naked dna method, and measured beta-gal activity in keratinocytes. the results showed that beta-galactosida ...	2000	10808128
alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4		2000	10811948
competitive binding to a charged leucine motif represses transformation by a papillomavirus e6 oncoprotein.	e6 oncoproteins from hpv-16 and bovine papillomavirus type 1 (bpv-1) bind to similar leucine-rich peptides termed charged leucine motifs found on the cellular focal adhesion protein paxillin and the e3 ubiquitin ligase e6ap. bpv-1 e6 (be6) mutants that do not bind to paxillin are defective at inducing cellular transformation. it is possible, however, that be6 mutants that do not bind paxillin are defective for transformation for an unrelated reason than the ability to bind to charged leucine mot ...	2000	10814581
amf-1/gps2 binds p300 and enhances its interaction with papillomavirus e2 proteins.	the cellular protein amf-1 (gps2) positively modulates gene expression by the papillomavirus e2 protein (d. e. breiding et al., mol. cell. biol. 17:7208-7219, 1997). we show here that amf-1 also binds the transcriptional coactivator p300 in vitro and in vivo. e2 interacted weakly with p300. these observations led to a model in which amf-1 recruits p300 into a complex with e2. cotransfection of amf-1 or p300 stimulated levels of e2-dependent transcription, while cotransfection of both amf-1 and p ...	2000	10846067
optimization of a weak 3' splice site counteracts the function of a bovine papillomavirus type 1 exonic splicing suppressor in vitro and in vivo.	alternative splicing is a critical component of the early to late switch in papillomavirus gene expression. in bovine papillomavirus type 1 (bpv-1), a switch in 3' splice site utilization from an early 3' splice site at nucleotide (nt) 3225 to a late-specific 3' splice site at nt 3605 is essential for expression of the major capsid (l1) mrna. three viral splicing elements have recently been identified between the two alternative 3' splice sites and have been shown to play an important role in th ...	2000	10846071
proteasome-mediated degradation of the papillomavirus e2-ta protein is regulated by phosphorylation and can modulate viral genome copy number.	the bovine papillomavirus e2 proteins regulate viral transcription, replication, and episomal genome maintenance. we have previously mapped the major phosphorylation sites of the e2 proteins to serine residues 298 and 301 and shown that mutation of serine residue 301 to alanine leads to a dramatic (10- to 20-fold) increase in viral dna copy number. in this study we analyzed how phosphorylation regulates e2 protein function. s301 is located in a pest sequence; these sequences are often found in p ...	2000	10846085
separate domains in e1 and e2 proteins serve architectural and productive roles for cooperative dna binding.	the e1 and e2 proteins from bovine papillomavirus bind cooperatively to binding sites in the viral origin of dna replication. the dna-binding domains (dbds) of the two proteins interact with each other, and the e2 transactivation domain interacts with the helicase domain of e1. mutations that disrupt the interaction between the two dbds also disrupt the interaction between the e2 activation domain and the e1 helicase domain, demonstrating interdependence of the two interactions. cooperative bind ...	2000	10856250
in vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus dna-carrying c3h/10t(1/2) cell line.	a new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an s-9 microsomal fraction for detection in the bacterial mutagenicity assay. the assay uses focus formation in a stable, bovine papillomavirus type 1 (bpv-1) dna carrying c3h/10t(1/2) mouse embryo fibroblast cell line (t1) that does not require transfection, infection with virus, ...	2000	10861948
bovine papillomavirus e1 protein is sumoylated by the host cell ubc9 protein.	papillomavirus e1 protein is the replication initiator that recognizes and binds to the viral origin and initiates dna strand separation through its atp-dependent helicase activity. the e1 protein also functions in viral dna replication by recruiting several cellular proteins to the origin, including host dna polymerase alpha and replication protein a. to identify other cellular proteins that interact with bovine papillomavirus e1, an hela cdna library was screened using a yeast two-hybrid assay ...	2000	10871618
bpv1 e2 protein enhances packaging of full-length plasmid dna in bpv1 pseudovirions.	we studied determinants of efficient encapsidation of circular dna, incorporating a pv early region dna sequence (nt 584-1978) previously shown to enhance packaging of dna within papillomavirus (pv)-like particles (vlps). insect coelomic cells (sf-9) and cultured monkey kidney cells (cos-1) were transfected with an 8-kb reporter plasmid incorporating the putative bpv packaging sequence and infected with bpv1 l1 and l2 recombinant baculovirus or vaccinia virus. heavy (1.34 g/ml) and light (1.30 g ...	2000	10873782
binding of the human papillomavirus type 16 e7 oncoprotein and the adeno-associated virus rep78 major regulatory protein in vitro and in yeast and the potential for downstream effects.	both human papillomavirus (hpv) and adeno-associated virus (aav) are common anogenital viruses and likely co-infect the epithelium in vivo. however, whereas hpvs are positively associated with cervical cancer, aav appears to be negatively associated. in tissue culture, aav-encoded rep78--which is essential for aav--inhibits gene expression and oncogenic transformation by hpv-16/18 and bovine papillomavirus type 1. here we observed whether the hpv-16 e7 oncoprotein might recognize and bind rep78. ...	2000	10881991
rb-independent induction of apoptosis by bovine papillomavirus type 1 e7 in response to tumor necrosis factor alpha.	bovine papillomavirus type 1 (bpv-1) is a small dna virus that causes fibropapillomas of the host. bpv-1 has served as the prototype for studies of the molecular biology of the papillomaviruses. bpv-1 efficiently induces anchorage-independent growth and focus formation in murine c127 cells. the transforming properties of bpv-1 primarily reside in two genes, e5 and e6. each of these genes is sufficient to transform cells. although no independent transformation activity has been detected for e7, i ...	2000	10887172
contribution of bovine papillomavirus type 1 e1 protein residue 48 to replication function.	the e1 protein of bovine papillomavirus type 1 (bpv-1) is the origin recognition protein and is essential for the initiation of viral dna replication. we reported previously that there is a conserved motif between residues 25 and 60 of all papillomavirus e1 proteins that resembles a casein kinase ii (ckii) phosphorylation site. the corresponding serine in bpv-1, serine-48, is an efficient substrate for ckii in vitro. to examine the functional role of this potential phosphorylation site, three am ...	2000	10900038
the structural basis of dna target discrimination by papillomavirus e2 proteins.	the papillomavirus e2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral dna replication. disruption of the e2 gene is commonly associated with malignancy in cervical carcinoma, indicating that e2 has a role in regulating tumor progression. although the e2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair dna sequence, the cancer-associated human papillomavirus e2 proteins display a unique ability to detect dna fl ...	2000	10906136
papillomavirus virus-like particles for the delivery of multiple cytotoxic t cell epitopes.	chimeric papillomavirus (pv) virus-like particles (vlps) based on the bovine papillomavirus type 1 (bpv-1) l1 protein were constructed by replacing the 23-carboxyl-terminal amino acids of the bpv1 major protein l1 with an artificial "polytope" minigene, containing known ctl epitopes of human pv16 e7 protein, hiv iiib gp120 p18, nef, and reverse transcriptase (rt) proteins, and an hpv16 e7 linear b epitope. the ctl epitopes were restricted by three different mhc class i alleles (h-2(b), h-2(d), h ...	2000	10915608
transformation of mortal human fibroblasts and activation of a growth inhibitory pathway by the bovine papillomavirus e5 oncoprotein.	the 44-amino acid bovine papillomavirus e5 protein induces tumorigenic transformation of immortal rodent fibroblasts by binding to and activating the platelet-derived growth factor beta receptor (pdgfbetar). here e5 was expressed in mortal human diploid fibroblasts (hdfs), which lack the accumulated genetic changes that are present in immortal rodent cells. e5 induced focus formation and morphological transformation of hdfs without inducing anchorage independence or immortalization. similar effe ...	2000	10939593
crystal structure of the dna binding domain of the replication initiation protein e1 from papillomavirus.	papillomaviral infection causes both benign and malignant lesions and is a necessary cause of cervical carcinoma. replication of this virus requires the replication initiation proteins e1 and e2, which bind cooperatively at the origin of replication (ori) as an (e1)2-(e2)2-dna complex. this is a precursor to larger e1 complexes that distort and unwind the ori. we present the crystal structure of the e1 dna binding domain refined to 1.9 a resolution. residues critical for dna binding are located ...	2000	10949036
n-butyrate mediated inhibition of papovavirus dna replication in vivo and in cell culture: a mechanistic approach.	n-butyrate, an inhibitor of g1-to-s transition inhibits papovavirus dna replication in cell culture. to explore the efficacy of n-butyrate in vivo and to better understand its mechanism, we studied the effect of n-butyrate on viral dna replication in mice acutely infected with polyomavirus and in the papovavirus-infected cells in culture. newborn mice treated with n-butyrate stop growing and become runted. when infected with polyomavirus, these mice show a strong overall inhibition of viral dna. ...	2000	10949947
relationship between retroviral dna integration and gene expression.	although retroviruses can integrate their dna into a large number of sites in the host genome, factors controlling the specificity of integration remain controversial and poorly understood. to assess the effects of transcriptional activity on integration in vivo, we created quail cell clones containing a construct with a minigene cassette, whose expression is controlled by the papilloma virus e2 protein. from these clones we derived transcriptionally active subclones expressing the wild-type e2 ...	2000	10954538
the platelet-derived growth factor beta receptor as a target of the bovine papillomavirus e5 protein.	the 44-amino acid e5 protein of bovine papillomavirus is a homo-dimeric, transmembrane protein that transforms cells by activating the platelet-derived growth factor ss receptor in a ligand-independent fashion. the e5 protein induces receptor activation by forming a stable complex with the receptor, thereby inducing receptor dimerization, trans-phosphorylation of tyrosine residues in the cytoplasmic domain of the receptor, and recruitment of cellular sh2 domain-containing proteins into a signal ...	2000	10959076
episomal vectors for gene expression in mammalian cells.	an important reason for preferring mammalian cells for heterologous gene expression is their ability to make authentic proteins containing post-translational modifications similar to those of the native protein. the development of expression systems for mammalian cells has been ongoing for several years, resulting in a wide variety of effective expression vectors. the aim of this review is to highlight episomal expression vectors. such episomal plasmids are usually based on sequences from dna vi ...	2000	10971576
e2f-rb complexes assemble and inhibit cdc25a transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression.	expression of the bovine papillomavirus e2 protein in cervical carcinoma cells represses expression of integrated human papillomavirus (hpv) e6/e7 oncogenes, followed by repression of the cdc25a gene and other cellular genes required for cell cycle progression, resulting in dramatic growth arrest. to explore the mechanism of repression of cell cycle genes in cervical carcinoma cells following e6/e7 repression, we analyzed regulation of the cdc25a promoter, which contains two consensus e2f bindin ...	2000	10982822
a recombinant vaccinia virus containing the papilloma e2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity.	human papillomavirus infection is associated with cervical cancer. the e6 and e7 papillomavirus proteins are normally required for the maintenance of the malignant phenotype. expression of these proteins in infected cells is negatively regulated by the binding of the papilloma e2 protein to the long terminal control region of the papilloma virus genome. the e2 protein can also promote cell arrest and apoptosis in hela cells. therefore, it is clear that this protein has the potential of inhibitin ...	2000	10999461
sumo-1 modification of bovine papillomavirus e1 protein is required for intranuclear accumulation.	the e1 protein is a multifunctional, origin-binding helicase that is essential for replication of papillomaviruses. recently, bovine papillomavirus e1 was shown to be post-translationally modified by the addition of the sumo-1 polypeptide. here we show that the site of sumoylation maps to lysine residue 514. this lysine and the flanking sequences are well conserved in human papillomavirus (hpv) e1 proteins. both hpv1a and hpv18 e1 proteins are substrates for sumoylation in vitro, which is consis ...	2000	11005821
rapid induction of senescence in human cervical carcinoma cells.	expression of the bovine papillomavirus e2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus e6 and e7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. this process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased tel ...	2000	11005870
interaction with cbp/p300 enables the bovine papillomavirus type 1 e6 oncoprotein to downregulate cbp/p300-mediated transactivation by p53.	the e6 oncoprotein of bovine papillomavirus type 1 (bpv-1) can transform cells independently of p53 degradation. the precise mechanisms underlying this transformation are not yet completely understood. here it is shown that bpv-1 e6 interacts with cbp/p300 in the same way as described for the e6 proteins of oncogenic human papillomaviruses. this interaction results in an inhibition of the transcriptional coactivator function of cbp/p300 required by p53 and probably by other transcription factors ...	2000	11038372
interaction of the papillomavirus transcription/replication factor, e2, and the viral capsid protein, l2.	the minor capsid protein l2 of papillomaviruses (pvs) likely plays a role in the selective encapsidation of pv dna in viral capsids and in the infectivity of pv virions. the l2 protein also can cause the relocalization of the pv early protein, e2ta, to nuclear subdomains known as promyelocytic leukemia oncogenic domains (pods) in which it is localized. e2ta is a transcriptional transactivator that also plays a critical role in viral dna replication. in this study, we investigated whether l2, in ...	2000	11040122
utilization of the bovine papillomavirus type 1 late-stage-specific nucleotide 3605 3' splice site is modulated by a novel exonic bipartite regulator but not by an intronic purine-rich element.	bovine papillomavirus type 1 (bpv-1) late gene expression is regulated at both transcriptional and posttranscriptional levels. maturation of the capsid protein (l1) pre-mrna requires a switch in 3' splice site utilization. this switch involves activation of the nucleotide (nt) 3605 3' splice site, which is utilized only in fully differentiated keratinocytes during late stages of the virus life cycle. our previous studies of the mechanisms that regulate bpv-1 alternative splicing identified three ...	2000	11044105