de Novo Structure Prediction (2008)
K. V. Holmes, In Fields Virology, P. M. Howley, X. Xiao, S. Chakraborti, ...
(2001). 13. W. Li et al., Nature 426, 450 (2003). 14. H. Hofmann et al., Proc. Natl. Acad. Sci. U.S.A. 102, 7988 (2005).
Khleif, S N, DeGregori, J, Yee, C L, Otterson, G A, Kaye, F J, Nevins, J R, ...
Alterations of various components of the cell cycle regulatory machinery that controls the progression of cells from a quiescent to a growing state contribute to the development of many human...
Arbeit, J M, Howley, P M, Hanahan, D
High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be...
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
Huibregtse, J M, Scheffner, M, Beaudenon, S, Howley, P M
E6-AP is a 100-kDa cellular protein that interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53...
Scheffner, M, Huibregtse, J M, Howley, P M
The E6 protein of the oncogenic human papillomavirus types 16 and 18 facilitates the rapid degradation of the tumor-suppressor protein p53 via the ubiquitin-dependent proteolytic pathway. The E6...
The "high-risk" human papillomavirus types 16 (HPV-16) and 18 (HPV-18) have been etiologically implicated in the majority of human cervical carcinomas. In these cancers, the viral DNAs are often...
Heck, D V, Yee, C L, Howley, P M, Münger, K
The human papillomaviruses (HPVs) associated with genital tract lesions can be classified as either "high risk" or "low risk" based on their association with human anogenital cancer. The E7 proteins...
Chellappan, S, Kraus, V B, Kroger, B, Munger, K, Howley, P M, Phelps, W C, ...
The adenovirus E1A gene product, the simian virus 40 large tumor antigen, and the human papillomavirus E7 protein share a short amino acid sequence that constitutes a domain required for the...
McBride, A A, Klausner, R D, Howley, P M
The bovine papillomavirus type 1 E2 open reading frame encodes three proteins involved in viral DNA replication and transcriptional regulation. These polypeptides share a carboxyl-terminal domain...
The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines.
Scheffner, M, Münger, K, Byrne, J C, Howley, P M
Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each...
Pietenpol, J A, Münger, K, Howley, P M, Stein, R W, Moses, H L
Previous studies have shown that transforming growth factor beta 1 (TGF-beta 1) inhibition of keratinocyte proliferation involves suppression of c-myc transcription, and indirect evidence has...
Ubiquitin conjugating enzymes (UBCs) are a family of proteins directly involved in ubiquitination of proteins. Ubiquitination is known to be involved in control of a variety of cellular processes,...
Rentier-Delrue, F, Lubiniecki, A, Howley, P M
Human polyomavirus JC DNA was purified directly from the diseased brain tissue of two patients with progressive multifocal leukoencephalopathy (PML) by a method employing differential salt...
Papillomaviruses induce benign squamous epithelial lesions that infrequently are associated with uncontrolled growth or malignant conversion. The virus-encoded oncogenes are clearly under negative...
Interaction between the E1 and E2 papillomavirus proteins appear to play an important role in viral DNA replication, although the exact domains of each protein involved in this interaction have not...
Suppression of cellular proliferation by the papillomavirus E2 protein.
Dowhanick, J J, McBride, A A, Howley, P M
Carcinogenic progression of a human papillomavirus (HPV)-infected cell is often associated with integration of the viral genome in a manner which results in the loss of expression of the viral...
Sakai, H, Yasugi, T, Benson, J D, Dowhanick, J J, Howley, P M
The E2 gene products of papillomavirus play key roles in viral replication, both as regulators of viral transcription and as auxiliary factors that act with E1 in viral DNA replication. We have...
Yasugi, T, Benson, J D, Sakai, H, Vidal, M, Howley, P M
The papillomavirus E1 and E2 proteins are both necessary and sufficient in vivo for efficient origin-dependent viral DNA replication. The ability of E1 and E2 to complex with each other appears to be...
Yasugi, T, Vidal, M, Sakai, H, Howley, P M, Benson, J D
Random mutagenesis of human papillomavirus type 16 (HPV16) E1 was used to generate E1 missense mutants defective for interaction with either hUBC9 or 16E1-BP, two cDNAs encoding proteins that have...
Benson, J D, Lawande, R, Howley, P M
Papillomavirus early gene expression is regulated by the virus gene-encoded E2 proteins. The best-characterized E2 protein, encoded by bovine papillomavirus type 1 (BPV-1), has been shown to interact...
Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation.
Levels of the tumor suppressor protein p53 are normally quite low due in part to its short half-life. p53 levels increase in cells exposed to DNA-damaging agents, such as radiation, and this increase...
Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.
Arbeit, J M, Münger, K, Howley, P M, Hanahan, D
To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in...
Spalholz, B A, Vande Pol, S B, Howley, P M
Transcriptional transactivation and repression by the viral E2 proteins are important regulatory mechanisms for the papillomaviruses. In the bovine papillomavirus type 1 (BPV-1), several viral...
Romanczuk, H, Villa, L L, Schlegel, R, Howley, P M
The human papillomavirus types 16 (HPV-16) and 18 (HPV-18) can immortalize primary human keratinocytes. The region of the viral genome responsible for this function maps to the E6 and E7 genes and...
Scheffner, M, Takahashi, T, Huibregtse, J M, Minna, J D, Howley, P M
The E6 oncoproteins encoded by the cancer-associated human papillomaviruses (HPVs) can associate with and promote the degradation of wild-type p53 in vitro. To gain further insight into this process,...
Münger, K, Yee, C L, Phelps, W C, Pietenpol, J A, Moses, H L, Howley, P M
Differences in the biological characteristics of the high-risk human papillomavirus type 16 (HPV-16) and the low-risk HPV-6 E7 proteins were analyzed and shown to correlate with certain biochemical...
Transient replication of human papillomavirus DNAs.
Del Vecchio, A M, Romanczuk, H, Howley, P M, Baker, C C
Information on papillomavirus DNA replication has primarily derived from studies with bovine papillomavirus type 1 (BPV-1). Our knowledge of DNA replication of the human papillomaviruses (HPVs) is...
The bovine papillomavirus type 1 long control region (LCR) contains DNA sequence elements involved in the regulation of viral transcription and replication. Differences in the levels of transcription...
Phenotypic analysis of bovine papillomavirus type 1 E2 repressor mutants.
Lambert, P F, Monk, B C, Howley, P M
The bovine papillomavirus type 1 (BPV-1) E2 open reading frame encodes three proteins: the E2 transcriptional transactivator, the E2 transcriptional repressor (E2-TR), and the E8/E2 fusion peptide....
Romanczuk, H, Thierry, F, Howley, P M
cis-Acting elements involved in E2 modulation of human papillomavirus type 16 (HPV-16) P97 promoter activity and HPV-18 P105 promoter activity were examined. In transfected primary human...
The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes at least three proteins with transcriptional regulatory properties. The full-length E2 open reading frame encodes a...
Phelps, W C, Bagchi, S, Barnes, J A, Raychaudhuri, P, Kraus, V, Münger, K, ...
The human papillomavirus E7 gene product is an oncoprotein with properties similar to those of the adenovirus E1A proteins. The human papillomavirus E7 proteins possess substantial amino acid...
Genetic assignment of multiple E2 gene products in bovine papillomavirus-transformed cells.
Lambert, P F, Hubbert, N L, Howley, P M, Schiller, J T
The E2 open reading frame of bovine papillomavirus type 1 has been shown genetically to encode at least three transcriptional regulatory factors, and three E2 specific proteins have been recently...
Münger, K, Phelps, W C, Bubb, V, Howley, P M, Schlegel, R
The early human papillomavirus type 16 genes that directly participate in the in vitro transformation of primary human keratinocytes have been defined. In the context of the full viral genome,...
Phosphorylation sites of the E2 transcriptional regulatory proteins of bovine papillomavirus type 1.
McBride, A A, Bolen, J B, Howley, P M
The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes three transcriptional regulatory proteins. The full-length open reading frame encodes a protein of 410 amino acids which...
Spalholz, B A, Byrne, J C, Howley, P M
The long control region of bovine papillomavirus type 1 (BPV-1) can function in an orientation- and position-independent manner as an E2-dependent enhancer. Dissection of the long control region has...
Bovine papillomavirus type 1 (BPV-1) is capable of replicating as a stable, high-copy-number plasmid in transformed rodent cells. The BPV-1 E1 open reading frame (ORF) encodes multiple functions...
Baker, C C, Phelps, W C, Lindgren, V, Braun, M J, Gonda, M A, Howley, P M
We cloned and analyzed the integrated human papillomavirus type 16 (HPV-16) genomes that are present in the human cervical carcinoma cell lines SiHa and CaSki. The single HPV-16 genome in the SiHa...
Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product.
We identified a conditional transcriptional enhancer in the long control region (LCR) of human papillomavirus type 16 (HPV-16). This conditional enhancer requires activation in trans by a product of...
Spalholz, B A, Lambert, P F, Yee, C L, Howley, P M
The long control region (LCR) of the bovine papillomavirus type 1 genome can function as a conditional transcriptional enhancer which can be specifically trans-activated by the viral E2 gene product....
Localization and analysis of bovine papillomavirus type 1 transforming functions.
Sarver, N, Rabson, M S, Yang, Y C, Byrne, J C, Howley, P M
Bovine papillomavirus type 1 (BPV-1) or cloned BPV-1 DNA can transform susceptible rodent cells, and the viral DNA remains as a stable extrachromosomal plasmid in the transformed cells. The...
Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes.
Danos, O, Engel, L W, Chen, E Y, Yaniv, M, Howley, P M
The DNA sequences of the genomes of the bovine type 1 and human type 1a papillomaviruses were compared. The overall organization of both genomes is very similar. Three areas of maximal homology were...
Maroteaux, L, Chen, L, Mitrani-Rosenbaum, S, Howley, P M, Revel, M
Mouse cells transformed by a bovine papillomavirus recombinant vector containing the human interferon (IFN) beta 1 (IFN-beta 1) gene could be induced to produce human as well as mouse IFNs. The...
Transcriptional organization of bovine papillomavirus type 1.
Engel, L W, Heilman, C A, Howley, P M
Multiple bovine papillomavirus type 1 (BPV-1)-specific polyadenylated RNA species in a BPV-1-infected bovine fibropapilloma were identified and mapped. All of the RNA species were transcribed from...
Functional analysis of the 3' open reading frames (ORFs) of bovine papillomavirus type 1 (BPV-1) has been complicated by the organization of that part of the genome. A region between nucleotides (nt)...
Schiffman, M H, Bauer, H M, Lorincz, A T, Manos, M M, Byrne, J C, Glass, A G, ...
A methodologic study was performed to compare the polymerase chain reaction (PCR) and Southern blot hybridization, two commonly used testing strategies for the detection of human papillomavirus (HPV)...
McBride, A A, Byrne, J C, Howley, P M
The E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV-1) encodes positive- and negative-acting factors that regulate viral gene expression. The full-length ORF encodes a...
Bovine papillomavirus type 1 3' early region transformation and plasmid maintenance functions.
Rabson, M S, Yee, C, Yang, Y C, Howley, P M
We examined bovine papillomavirus type 1 (BPV-1) DNAs mutated in the E2 open reading frame (ORF) to determine their ability (i) to transform C127 cells and (ii) to remain extrachromosomal in...
Bovine papillomavirus type 1 (BPV-1) has served as the prototype papillomavirus for the study of viral transcription, DNA replication, and latency. However, no cis essential transcription control...
Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein.
Phelps, W C, Münger, K, Yee, C L, Barnes, J A, Howley, P M
The E7 gene of human papillomavirus type 16 encodes a multifunctional nuclear phosphoprotein that is functionally and structurally similar to the adenovirus (Ad) E1A proteins and the T antigens of...
Lindgren, V, Sippola-Thiele, M, Skowronski, J, Wetzel, E, Howley, P M, Hanahan, D
In the BPV1.69 line of transgenic mice, the bovine papillomavirus type 1 genome elicits both benign dermal fibroblastic proliferation (fibromatoses) and malignant fibrosarcomas. Because these lesions...
Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences.
Law, M F, Lowy, D R, Dvoretzky, I, Howley, P M
The viral DNA sequences in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV-1) virions, by full-length linear BPV-1 DNA, or by a defined transforming subgenomic DNA segment of BPV-1...
Sarver, N, Byrne, J C, Howley, P M
The unique ability of bovine papillomavirus (BPV-1) DNA to replicate as a stable, multicopy plasmid in transformed mouse cells has led to its utilization as a eukaryotic cloning vector. One...
Turek, L P, Byrne, J C, Lowy, D R, Dvoretzky, I, Friedman, R M, Howley, P M
The effect of mouse L-cell interferon on bovine papillomavirus type 1 (BPV-1) transformation of murine cells was examined. Mouse interferon reduced the level of BPV-1-induced transformation of mouse...
Characterization of the genome of the murine papovavirus K.
Law, M F, Takemoto, K K, Howley, P M
The DNA genome of the murine papovavirus K virus (KV) was characterized and compared with the genome of polyoma virus. A physical map of the KV genome was constructed by analysis of the size of DNA...
JC human papovavirus replication in human amnion cells.
Takemoto, K K, Howley, P M, Miyamura, T
JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological methods as JC virus. By restriction...
Identification of the primate papovavirus HD as the stump-tailed macaque virus.
Howley, P M, Newell, N, Shah, K V, Law, M F, Gruss, P, Sauer, G, ...
The recently isolated primate papovavirus HD is shown to be indistinguishable from the stump-tailed macaque virus by immunofluorescent reactivity, by restriction endonuclease analysis, and by nucleic...
Conserved polynucleotide sequences among the genomes of papillomaviruses.
Law, M F, Lancaster, W D, Howley, P M
The DNAs of different members of the Papillomavirus genus of papovaviruses were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm - 28 degrees C), no homology was...
Cloning of human papilloma virus genomic DNAs and analysis of homologous polynucleotide sequences.
Heilman, C A, Law, M F, Israel, M A, Howley, P M
The complete DNA genomes of four distinct human papilloma viruses (human papilloma virus subtype 1a [HPV-1a], HPV-1b, HPV-2a, and HPV-4) were molecularly cloned in Escherichia coli, using the...
Cloned human polyomavirus JC DNA can transform human amnion cells.
Howley, P M, Rentier-Delrue, F, Heilman, C A, Law, M F, Chowdhury, K, Israel, M A, ...
The genome of the human polyomavirus JC (Mad-1 strain) was molecularly cloned in Escherichia coli by using the plasmid vector pBR322. Recombinant DNA molecules were constructed with the entire JC...
Characterization of K virus and its comparison with polyoma virus.
Bond, S B, Howley, P M, Takemoto, K K
The antigenic relationship between the two murine papovaviruses, K virus and polyoma virus, was examined by serological techniques to determine whether they shared any antigenic components. No...
Characterization of human papovavirus BK DNA.
Howley, P M, Mullarkey, M F, Takemoto, K K, Martin, M A
The DNA of the BK virus (BKV) human papovavirus was found to be heterogeneous, consisting of at least four discrete species of DNA. Only the largest of these four species, BKV DNA (i), which has a...
Physical map of the BK virus genome.
Howley, P M, Khoury, G, Byrne, J C, Takemoto, K K, Martin, M A
Two new human papovavirus isolates (JMV and MMV) from the urines of patients with Wiskott-Aldrich syndrome were morphologically and serologically identical to BK virus (BKV). The genomes of these two...
Huibregtse, J M, Scheffner, M, Howley, P M
The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and...
Huibregtse, J M, Scheffner, M, Howley, P M
E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific...
Unger, T, Mietz, J A, Scheffner, M, Yee, C L, Howley, P M
The wild-type (wt) p53 protein has transcriptional activation functions which may be linked to its tumor suppressor activity. Many mutant p53 proteins expressed in cancers have lost the ability to...
Sippola-Thiele, M, Hanahan, D, Howley, P M
Tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the BPV-1 genome was found to involve distinct proliferative stages. Cell cultures derived from normal skin, from benign...
Novel method for identifying sequence-specific DNA-binding proteins.
We developed a general method for the enrichment and identification of sequence-specific DNA-binding proteins. A well-characterized protein-DNA interaction is used to isolate from crude cellular...
Mitrani-Rosenbaum, S, Maroteaux, L, Mory, Y, Revel, M, Howley, P M
A 1.6-kilobase DNA segment of the genomic human interferon beta 1 (IF-beta 1) gene was inserted into each of two possible orientations at the single HindIII site of a recombinant plasmid pBPV69T,...
Howley, P M, Schenborn, E T, Lund, E, Byrne, J C, Dahlberg, J E
We constructed a mutant of bovine papillomavirus type 1 (BPV-1) DNA that lacked a transcriptional enhancer located 3' to the polyadenylation site of the early viral RNAs expressed in transformed...
Eiden, M, Newman, M, Fisher, A G, Mann, D L, Howley, P M, Reitz, M S
In an attempt to express the small (transmembrane) envelope protein p21e of type 1 human T-cell leukemia (lymphotrophic) virus (HTLV-1) exclusive of other viral gene products, we have constructed a...
Enhancer-dependent expression of the rat preproinsulin gene in bovine papillomavirus type 1 vectors.
Sarver, N, Muschel, R, Byrne, J C, Khoury, G, Howley, P M
The effect of position in a bovine papillomavirus type 1 (BPV-1) vector on foreign gene expression was assessed with the rat preproinsulin (rI1) gene. The rI1 gene was inserted at each of the...
Bovine papilloma virus deoxyribonucleic acid: a novel eucaryotic cloning vector.
Sarver, N, Gruss, P, Law, M F, Khoury, G, Howley, P M
A novel eucaryotic vector derived from the transforming region of bovine papilloma virus was established and demonstrated to be highly effective for introducing foreign genes into animal cells. The...
A stable bovine papillomavirus hybrid plasmid that expresses a dominant selective trait.
Law, M F, Byrne, J C, Howley, P M
We describe a bovine papillomavirus hybrid plasmid containing the neomycin resistance gene from Tn5 inserted into a mammalian cell transcriptional unit. This plasmid is maintained as a stable...
Small, J A, Khoury, G, Jay, G, Howley, P M, Scangos, G A
JC virus and BK virus are ubiquitous human viruses that share sequence and structural homology with simian virus 40. To characterize tissue-specific expression of these viruses and to establish model...
Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.
Gendelman, H E, Phelps, W, Feigenbaum, L, Ostrove, J M, Adachi, A, Howley, P M, ...
To investigate whether DNA viruses can augment gene expression of the human immunodeficiency virus (HIV), cotransfection experiments were carried out in which a recombinant plasmid containing the HIV...
Bovine papillomavirus contains multiple transforming genes.
Yang, Y C, Okayama, H, Howley, P M
Bovine papillomavirus type 1 (BPV-1) and its cloned full-length DNA can transform rodent cells in vitro, and the viral DNA persists as an extrachromosomal multicopy plasmid in these transformed...
Münger, K, Werness, B A, Dyson, N, Phelps, W C, Harlow, E, Howley, P M
The E7 proteins encoded by the human papillomaviruses (HPVs) associated with anogenital lesions share significant amino acid sequence homology. The E7 proteins of these different HPVs were assessed...
Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40.
Khoury, G, Howley, P M, Garon, C, Mullarkey, M F, Takemoto, K K, Martin, M A
A number of hybridization techniques have been used to assess the homology between the genomes of BK virus (BKV) and simian virus 40 (SV40). A noncontiguous set of homologous sequences has been...
Huibregtse, J M, Scheffner, M, Howley, P M
The E6 protein of human papillomavirus types 16 and 18 (HPV-16 and HPV-18) can stably associate with the p53 protein in vitro. In the presence of rabbit reticulocyte lysate, this association leads to...
McBride, A A, Schlegel, R, Howley, P M
The E2 open reading frame of bovine papilloma virus 1 (BPV-1) has been shown to encode both positive and negative acting transcriptional regulatory factors. The DNA binding properties of these...
The bovine papillomavirus P2443 promoter is E2 trans-responsive: evidence for E2 autoregulation.
Hermonat, P L, Spalholz, B A, Howley, P M
The bovine papillomavirus type 1 (BPV-1) P2443 promoter is located just upstream of the E2, E3, E4 and E5 open reading frames (ORFs) and is active in both transformed rodent cells and in productively...
Genome localization of simian virus 40 RNA species.
Khoury, G, Carter, B J, Ferdinand, F J, Howley, P M, Brown, M, Martin, M A
The topographical locations on the simian virus 40 (SV40) genome of the templates for virus-specific RNA species present late in the lytic infection were determined by RNA-DNA hybridization...
Uniform representation of the human papovavirus BK genome in transformed hamster cells.
The DNA of three cloned lines of hamster kidney cells transformed by human papovavirus BK DNA was examined by reassociation kinetics for viral sequences and found to contain 2.7 to 5.3 equivalents of...
Expression of the 'late' genes of bovine papillomavirus type 1 (BPV-1) occurs only in the differentiated keratinocytes of the productively infected fibropapilloma. A detailed analysis of viral...
Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.
Scheffner, M, Münger, K, Huibregtse, J M, Howley, P M
The E6 and the E7 proteins of the oncogenic human papillomavirus types 16 and 18 can stably associate with p53 and the retinoblastoma protein, respectively. The E6-p53 interaction results in the...
Mietz, J A, Unger, T, Huibregtse, J M, Howley, P M
The observed interaction between p53 and the oncoproteins encoded by several DNA tumor viruses suggests that these viruses mediate their transforming activities at least in part by altering the...
Benson, J D, Benson, M, Howley, P M, Struhl, K
The NOT genes were originally identified in a yeast genetic screen that selected mutations resulting in increased utilization of a non-consensus TC TATA element of the HIS3 promoter. Here, we present...
Khleif, S N, DeGregori, J, Yee, C L, Otterson, G A, Kaye, F J, Nevins, J R, ...
Alterations of various components of the cell cycle regulatory machinery that controls the progression of cells from a quiescent to a growing state contribute to the development of many human...
Arbeit, J M, Howley, P M, Hanahan, D
High-risk human papillomaviruses (HPVs), including type 16, have been identified as factors in cervical carcinogenesis. However, the presence and expression of the virus per se appear to be...
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
Huibregtse, J M, Scheffner, M, Beaudenon, S, Howley, P M
E6-AP is a 100-kDa cellular protein that interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53...
Scheffner, M, Huibregtse, J M, Howley, P M
The E6 protein of the oncogenic human papillomavirus types 16 and 18 facilitates the rapid degradation of the tumor-suppressor protein p53 via the ubiquitin-dependent proteolytic pathway. The E6...
The "high-risk" human papillomavirus types 16 (HPV-16) and 18 (HPV-18) have been etiologically implicated in the majority of human cervical carcinomas. In these cancers, the viral DNAs are often...
Heck, D V, Yee, C L, Howley, P M, Münger, K
The human papillomaviruses (HPVs) associated with genital tract lesions can be classified as either "high risk" or "low risk" based on their association with human anogenital cancer. The E7 proteins...
Chellappan, S, Kraus, V B, Kroger, B, Munger, K, Howley, P M, Phelps, W C, ...
The adenovirus E1A gene product, the simian virus 40 large tumor antigen, and the human papillomavirus E7 protein share a short amino acid sequence that constitutes a domain required for the...
McBride, A A, Klausner, R D, Howley, P M
The bovine papillomavirus type 1 E2 open reading frame encodes three proteins involved in viral DNA replication and transcriptional regulation. These polypeptides share a carboxyl-terminal domain...
The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines.
Scheffner, M, Münger, K, Byrne, J C, Howley, P M
Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each...
Pietenpol, J A, Münger, K, Howley, P M, Stein, R W, Moses, H L
Previous studies have shown that transforming growth factor beta 1 (TGF-beta 1) inhibition of keratinocyte proliferation involves suppression of c-myc transcription, and indirect evidence has...
Ubiquitin conjugating enzymes (UBCs) are a family of proteins directly involved in ubiquitination of proteins. Ubiquitination is known to be involved in control of a variety of cellular processes,...
Rentier-Delrue, F, Lubiniecki, A, Howley, P M
Human polyomavirus JC DNA was purified directly from the diseased brain tissue of two patients with progressive multifocal leukoencephalopathy (PML) by a method employing differential salt...
Papillomaviruses induce benign squamous epithelial lesions that infrequently are associated with uncontrolled growth or malignant conversion. The virus-encoded oncogenes are clearly under negative...
Interaction between the E1 and E2 papillomavirus proteins appear to play an important role in viral DNA replication, although the exact domains of each protein involved in this interaction have not...
Suppression of cellular proliferation by the papillomavirus E2 protein.
Dowhanick, J J, McBride, A A, Howley, P M
Carcinogenic progression of a human papillomavirus (HPV)-infected cell is often associated with integration of the viral genome in a manner which results in the loss of expression of the viral...
Sakai, H, Yasugi, T, Benson, J D, Dowhanick, J J, Howley, P M
The E2 gene products of papillomavirus play key roles in viral replication, both as regulators of viral transcription and as auxiliary factors that act with E1 in viral DNA replication. We have...
Yasugi, T, Benson, J D, Sakai, H, Vidal, M, Howley, P M
The papillomavirus E1 and E2 proteins are both necessary and sufficient in vivo for efficient origin-dependent viral DNA replication. The ability of E1 and E2 to complex with each other appears to be...
Yasugi, T, Vidal, M, Sakai, H, Howley, P M, Benson, J D
Random mutagenesis of human papillomavirus type 16 (HPV16) E1 was used to generate E1 missense mutants defective for interaction with either hUBC9 or 16E1-BP, two cDNAs encoding proteins that have...
Benson, J D, Lawande, R, Howley, P M
Papillomavirus early gene expression is regulated by the virus gene-encoded E2 proteins. The best-characterized E2 protein, encoded by bovine papillomavirus type 1 (BPV-1), has been shown to interact...
Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation.
Levels of the tumor suppressor protein p53 are normally quite low due in part to its short half-life. p53 levels increase in cells exposed to DNA-damaging agents, such as radiation, and this increase...
Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.
Arbeit, J M, Münger, K, Howley, P M, Hanahan, D
To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in...
Spalholz, B A, Vande Pol, S B, Howley, P M
Transcriptional transactivation and repression by the viral E2 proteins are important regulatory mechanisms for the papillomaviruses. In the bovine papillomavirus type 1 (BPV-1), several viral...
Romanczuk, H, Villa, L L, Schlegel, R, Howley, P M
The human papillomavirus types 16 (HPV-16) and 18 (HPV-18) can immortalize primary human keratinocytes. The region of the viral genome responsible for this function maps to the E6 and E7 genes and...
Scheffner, M, Takahashi, T, Huibregtse, J M, Minna, J D, Howley, P M
The E6 oncoproteins encoded by the cancer-associated human papillomaviruses (HPVs) can associate with and promote the degradation of wild-type p53 in vitro. To gain further insight into this process,...
Münger, K, Yee, C L, Phelps, W C, Pietenpol, J A, Moses, H L, Howley, P M
Differences in the biological characteristics of the high-risk human papillomavirus type 16 (HPV-16) and the low-risk HPV-6 E7 proteins were analyzed and shown to correlate with certain biochemical...
Transient replication of human papillomavirus DNAs.
Del Vecchio, A M, Romanczuk, H, Howley, P M, Baker, C C
Information on papillomavirus DNA replication has primarily derived from studies with bovine papillomavirus type 1 (BPV-1). Our knowledge of DNA replication of the human papillomaviruses (HPVs) is...
The bovine papillomavirus type 1 long control region (LCR) contains DNA sequence elements involved in the regulation of viral transcription and replication. Differences in the levels of transcription...
Phenotypic analysis of bovine papillomavirus type 1 E2 repressor mutants.
Lambert, P F, Monk, B C, Howley, P M
The bovine papillomavirus type 1 (BPV-1) E2 open reading frame encodes three proteins: the E2 transcriptional transactivator, the E2 transcriptional repressor (E2-TR), and the E8/E2 fusion peptide....
Romanczuk, H, Thierry, F, Howley, P M
cis-Acting elements involved in E2 modulation of human papillomavirus type 16 (HPV-16) P97 promoter activity and HPV-18 P105 promoter activity were examined. In transfected primary human...
The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes at least three proteins with transcriptional regulatory properties. The full-length E2 open reading frame encodes a...
Phelps, W C, Bagchi, S, Barnes, J A, Raychaudhuri, P, Kraus, V, Münger, K, ...
The human papillomavirus E7 gene product is an oncoprotein with properties similar to those of the adenovirus E1A proteins. The human papillomavirus E7 proteins possess substantial amino acid...
Genetic assignment of multiple E2 gene products in bovine papillomavirus-transformed cells.
Lambert, P F, Hubbert, N L, Howley, P M, Schiller, J T
The E2 open reading frame of bovine papillomavirus type 1 has been shown genetically to encode at least three transcriptional regulatory factors, and three E2 specific proteins have been recently...
Münger, K, Phelps, W C, Bubb, V, Howley, P M, Schlegel, R
The early human papillomavirus type 16 genes that directly participate in the in vitro transformation of primary human keratinocytes have been defined. In the context of the full viral genome,...
Phosphorylation sites of the E2 transcriptional regulatory proteins of bovine papillomavirus type 1.
McBride, A A, Bolen, J B, Howley, P M
The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes three transcriptional regulatory proteins. The full-length open reading frame encodes a protein of 410 amino acids which...
Spalholz, B A, Byrne, J C, Howley, P M
The long control region of bovine papillomavirus type 1 (BPV-1) can function in an orientation- and position-independent manner as an E2-dependent enhancer. Dissection of the long control region has...
Bovine papillomavirus type 1 (BPV-1) is capable of replicating as a stable, high-copy-number plasmid in transformed rodent cells. The BPV-1 E1 open reading frame (ORF) encodes multiple functions...
Baker, C C, Phelps, W C, Lindgren, V, Braun, M J, Gonda, M A, Howley, P M
We cloned and analyzed the integrated human papillomavirus type 16 (HPV-16) genomes that are present in the human cervical carcinoma cell lines SiHa and CaSki. The single HPV-16 genome in the SiHa...
Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product.
We identified a conditional transcriptional enhancer in the long control region (LCR) of human papillomavirus type 16 (HPV-16). This conditional enhancer requires activation in trans by a product of...
Spalholz, B A, Lambert, P F, Yee, C L, Howley, P M
The long control region (LCR) of the bovine papillomavirus type 1 genome can function as a conditional transcriptional enhancer which can be specifically trans-activated by the viral E2 gene product....
Localization and analysis of bovine papillomavirus type 1 transforming functions.
Sarver, N, Rabson, M S, Yang, Y C, Byrne, J C, Howley, P M
Bovine papillomavirus type 1 (BPV-1) or cloned BPV-1 DNA can transform susceptible rodent cells, and the viral DNA remains as a stable extrachromosomal plasmid in the transformed cells. The...
Comparative analysis of the human type 1a and bovine type 1 papillomavirus genomes.
Danos, O, Engel, L W, Chen, E Y, Yaniv, M, Howley, P M
The DNA sequences of the genomes of the bovine type 1 and human type 1a papillomaviruses were compared. The overall organization of both genomes is very similar. Three areas of maximal homology were...
Maroteaux, L, Chen, L, Mitrani-Rosenbaum, S, Howley, P M, Revel, M
Mouse cells transformed by a bovine papillomavirus recombinant vector containing the human interferon (IFN) beta 1 (IFN-beta 1) gene could be induced to produce human as well as mouse IFNs. The...
Transcriptional organization of bovine papillomavirus type 1.
Engel, L W, Heilman, C A, Howley, P M
Multiple bovine papillomavirus type 1 (BPV-1)-specific polyadenylated RNA species in a BPV-1-infected bovine fibropapilloma were identified and mapped. All of the RNA species were transcribed from...
Functional analysis of the 3' open reading frames (ORFs) of bovine papillomavirus type 1 (BPV-1) has been complicated by the organization of that part of the genome. A region between nucleotides (nt)...
Schiffman, M H, Bauer, H M, Lorincz, A T, Manos, M M, Byrne, J C, Glass, A G, ...
A methodologic study was performed to compare the polymerase chain reaction (PCR) and Southern blot hybridization, two commonly used testing strategies for the detection of human papillomavirus (HPV)...
McBride, A A, Byrne, J C, Howley, P M
The E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV-1) encodes positive- and negative-acting factors that regulate viral gene expression. The full-length ORF encodes a...
Bovine papillomavirus type 1 3' early region transformation and plasmid maintenance functions.
Rabson, M S, Yee, C, Yang, Y C, Howley, P M
We examined bovine papillomavirus type 1 (BPV-1) DNAs mutated in the E2 open reading frame (ORF) to determine their ability (i) to transform C127 cells and (ii) to remain extrachromosomal in...
Bovine papillomavirus type 1 (BPV-1) has served as the prototype papillomavirus for the study of viral transcription, DNA replication, and latency. However, no cis essential transcription control...
Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein.
Phelps, W C, Münger, K, Yee, C L, Barnes, J A, Howley, P M
The E7 gene of human papillomavirus type 16 encodes a multifunctional nuclear phosphoprotein that is functionally and structurally similar to the adenovirus (Ad) E1A proteins and the T antigens of...
Lindgren, V, Sippola-Thiele, M, Skowronski, J, Wetzel, E, Howley, P M, Hanahan, D
In the BPV1.69 line of transgenic mice, the bovine papillomavirus type 1 genome elicits both benign dermal fibroblastic proliferation (fibromatoses) and malignant fibrosarcomas. Because these lesions...
Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences.
Law, M F, Lowy, D R, Dvoretzky, I, Howley, P M
The viral DNA sequences in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV-1) virions, by full-length linear BPV-1 DNA, or by a defined transforming subgenomic DNA segment of BPV-1...
Sarver, N, Byrne, J C, Howley, P M
The unique ability of bovine papillomavirus (BPV-1) DNA to replicate as a stable, multicopy plasmid in transformed mouse cells has led to its utilization as a eukaryotic cloning vector. One...
Turek, L P, Byrne, J C, Lowy, D R, Dvoretzky, I, Friedman, R M, Howley, P M
The effect of mouse L-cell interferon on bovine papillomavirus type 1 (BPV-1) transformation of murine cells was examined. Mouse interferon reduced the level of BPV-1-induced transformation of mouse...
Characterization of the genome of the murine papovavirus K.
Law, M F, Takemoto, K K, Howley, P M
The DNA genome of the murine papovavirus K virus (KV) was characterized and compared with the genome of polyoma virus. A physical map of the KV genome was constructed by analysis of the size of DNA...
JC human papovavirus replication in human amnion cells.
Takemoto, K K, Howley, P M, Miyamura, T
JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological methods as JC virus. By restriction...
Identification of the primate papovavirus HD as the stump-tailed macaque virus.
Howley, P M, Newell, N, Shah, K V, Law, M F, Gruss, P, Sauer, G, ...
The recently isolated primate papovavirus HD is shown to be indistinguishable from the stump-tailed macaque virus by immunofluorescent reactivity, by restriction endonuclease analysis, and by nucleic...
Conserved polynucleotide sequences among the genomes of papillomaviruses.
Law, M F, Lancaster, W D, Howley, P M
The DNAs of different members of the Papillomavirus genus of papovaviruses were analyzed for nucleotide sequence homology. Under standard hybridization conditions (Tm - 28 degrees C), no homology was...
Cloning of human papilloma virus genomic DNAs and analysis of homologous polynucleotide sequences.
Heilman, C A, Law, M F, Israel, M A, Howley, P M
The complete DNA genomes of four distinct human papilloma viruses (human papilloma virus subtype 1a [HPV-1a], HPV-1b, HPV-2a, and HPV-4) were molecularly cloned in Escherichia coli, using the...
Cloned human polyomavirus JC DNA can transform human amnion cells.
Howley, P M, Rentier-Delrue, F, Heilman, C A, Law, M F, Chowdhury, K, Israel, M A, ...
The genome of the human polyomavirus JC (Mad-1 strain) was molecularly cloned in Escherichia coli by using the plasmid vector pBR322. Recombinant DNA molecules were constructed with the entire JC...
Characterization of K virus and its comparison with polyoma virus.
Bond, S B, Howley, P M, Takemoto, K K
The antigenic relationship between the two murine papovaviruses, K virus and polyoma virus, was examined by serological techniques to determine whether they shared any antigenic components. No...
Characterization of human papovavirus BK DNA.
Howley, P M, Mullarkey, M F, Takemoto, K K, Martin, M A
The DNA of the BK virus (BKV) human papovavirus was found to be heterogeneous, consisting of at least four discrete species of DNA. Only the largest of these four species, BKV DNA (i), which has a...
Physical map of the BK virus genome.
Howley, P M, Khoury, G, Byrne, J C, Takemoto, K K, Martin, M A
Two new human papovavirus isolates (JMV and MMV) from the urines of patients with Wiskott-Aldrich syndrome were morphologically and serologically identical to BK virus (BKV). The genomes of these two...
Huibregtse, J M, Scheffner, M, Howley, P M
The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and...
Huibregtse, J M, Scheffner, M, Howley, P M
E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific...
Unger, T, Mietz, J A, Scheffner, M, Yee, C L, Howley, P M
The wild-type (wt) p53 protein has transcriptional activation functions which may be linked to its tumor suppressor activity. Many mutant p53 proteins expressed in cancers have lost the ability to...
Sippola-Thiele, M, Hanahan, D, Howley, P M
Tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the BPV-1 genome was found to involve distinct proliferative stages. Cell cultures derived from normal skin, from benign...
Novel method for identifying sequence-specific DNA-binding proteins.
We developed a general method for the enrichment and identification of sequence-specific DNA-binding proteins. A well-characterized protein-DNA interaction is used to isolate from crude cellular...
Mitrani-Rosenbaum, S, Maroteaux, L, Mory, Y, Revel, M, Howley, P M
A 1.6-kilobase DNA segment of the genomic human interferon beta 1 (IF-beta 1) gene was inserted into each of two possible orientations at the single HindIII site of a recombinant plasmid pBPV69T,...
Howley, P M, Schenborn, E T, Lund, E, Byrne, J C, Dahlberg, J E
We constructed a mutant of bovine papillomavirus type 1 (BPV-1) DNA that lacked a transcriptional enhancer located 3' to the polyadenylation site of the early viral RNAs expressed in transformed...
Eiden, M, Newman, M, Fisher, A G, Mann, D L, Howley, P M, Reitz, M S
In an attempt to express the small (transmembrane) envelope protein p21e of type 1 human T-cell leukemia (lymphotrophic) virus (HTLV-1) exclusive of other viral gene products, we have constructed a...
Enhancer-dependent expression of the rat preproinsulin gene in bovine papillomavirus type 1 vectors.
Sarver, N, Muschel, R, Byrne, J C, Khoury, G, Howley, P M
The effect of position in a bovine papillomavirus type 1 (BPV-1) vector on foreign gene expression was assessed with the rat preproinsulin (rI1) gene. The rI1 gene was inserted at each of the...
Bovine papilloma virus deoxyribonucleic acid: a novel eucaryotic cloning vector.
Sarver, N, Gruss, P, Law, M F, Khoury, G, Howley, P M
A novel eucaryotic vector derived from the transforming region of bovine papilloma virus was established and demonstrated to be highly effective for introducing foreign genes into animal cells. The...
A stable bovine papillomavirus hybrid plasmid that expresses a dominant selective trait.
Law, M F, Byrne, J C, Howley, P M
We describe a bovine papillomavirus hybrid plasmid containing the neomycin resistance gene from Tn5 inserted into a mammalian cell transcriptional unit. This plasmid is maintained as a stable...
Small, J A, Khoury, G, Jay, G, Howley, P M, Scangos, G A
JC virus and BK virus are ubiquitous human viruses that share sequence and structural homology with simian virus 40. To characterize tissue-specific expression of these viruses and to establish model...
Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.
Gendelman, H E, Phelps, W, Feigenbaum, L, Ostrove, J M, Adachi, A, Howley, P M, ...
To investigate whether DNA viruses can augment gene expression of the human immunodeficiency virus (HIV), cotransfection experiments were carried out in which a recombinant plasmid containing the HIV...
Bovine papillomavirus contains multiple transforming genes.
Yang, Y C, Okayama, H, Howley, P M
Bovine papillomavirus type 1 (BPV-1) and its cloned full-length DNA can transform rodent cells in vitro, and the viral DNA persists as an extrachromosomal multicopy plasmid in these transformed...
Münger, K, Werness, B A, Dyson, N, Phelps, W C, Harlow, E, Howley, P M
The E7 proteins encoded by the human papillomaviruses (HPVs) associated with anogenital lesions share significant amino acid sequence homology. The E7 proteins of these different HPVs were assessed...
Homology and relationship between the genomes of papovaviruses, BK virus and simian virus 40.
Khoury, G, Howley, P M, Garon, C, Mullarkey, M F, Takemoto, K K, Martin, M A
A number of hybridization techniques have been used to assess the homology between the genomes of BK virus (BKV) and simian virus 40 (SV40). A noncontiguous set of homologous sequences has been...
Huibregtse, J M, Scheffner, M, Howley, P M
The E6 protein of human papillomavirus types 16 and 18 (HPV-16 and HPV-18) can stably associate with the p53 protein in vitro. In the presence of rabbit reticulocyte lysate, this association leads to...
McBride, A A, Schlegel, R, Howley, P M
The E2 open reading frame of bovine papilloma virus 1 (BPV-1) has been shown to encode both positive and negative acting transcriptional regulatory factors. The DNA binding properties of these...
The bovine papillomavirus P2443 promoter is E2 trans-responsive: evidence for E2 autoregulation.
Hermonat, P L, Spalholz, B A, Howley, P M
The bovine papillomavirus type 1 (BPV-1) P2443 promoter is located just upstream of the E2, E3, E4 and E5 open reading frames (ORFs) and is active in both transformed rodent cells and in productively...
Genome localization of simian virus 40 RNA species.
Khoury, G, Carter, B J, Ferdinand, F J, Howley, P M, Brown, M, Martin, M A
The topographical locations on the simian virus 40 (SV40) genome of the templates for virus-specific RNA species present late in the lytic infection were determined by RNA-DNA hybridization...
Uniform representation of the human papovavirus BK genome in transformed hamster cells.
The DNA of three cloned lines of hamster kidney cells transformed by human papovavirus BK DNA was examined by reassociation kinetics for viral sequences and found to contain 2.7 to 5.3 equivalents of...
Expression of the 'late' genes of bovine papillomavirus type 1 (BPV-1) occurs only in the differentiated keratinocytes of the productively infected fibropapilloma. A detailed analysis of viral...
Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.
Scheffner, M, Münger, K, Huibregtse, J M, Howley, P M
The E6 and the E7 proteins of the oncogenic human papillomavirus types 16 and 18 can stably associate with p53 and the retinoblastoma protein, respectively. The E6-p53 interaction results in the...
Mietz, J A, Unger, T, Huibregtse, J M, Howley, P M
The observed interaction between p53 and the oncoproteins encoded by several DNA tumor viruses suggests that these viruses mediate their transforming activities at least in part by altering the...
Benson, J D, Benson, M, Howley, P M, Struhl, K
The NOT genes were originally identified in a yeast genetic screen that selected mutations resulting in increased utilization of a non-consensus TC TATA element of the HIS3 promoter. Here, we present...
Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs.
Arbeit, J. M., Münger, K., Howley, P. M., Hanahan, D.
The effect of the human papillomavirus (HPV) oncogenes E6 and E7 was examined in transgenic mice with a construct containing the human beta-actin promoter regulating HPV16 E6 and E7 open reading...
Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines.
Yee, C., Krishnan-Hewlett, I., Baker, C. C., Schlegel, R., Howley, P. M.
A series of human carcinoma cell lines was examined for human papillomavirus (HPV) DNA sequences with the use of HPV-6, HPV-11, HPV-16, and HPV-18 DNA probes. Six of eight cell lines derived from...