Genetic analysis of the 3′ early region transformation and replication functions of bovine papillomavirus type 1

Groff, Dennis E.; Lancaster, Wayne D.

doi:10.1016/0042-6822(86)90281-3

Cited by 101 publications

(71 citation statements)

References 16 publications

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“…There are several candidate viral genes for this biological effect, including the papillomavirus E5, E6 and E7 genes which have been shown to have demonstrable transforming activity in rodent cell assays (Bedell et al, 1987;Schiller et al, 1985Schiller et al, , 1986Groff and Lancaster, 1986;DiMaio et al, 1986;Yang et al, 1985a,b). Recently, the E5 protein of bovine papillomavirus was shown to exhibit mitogenic activity when microinjected into mouse cells (Green and Loewenstein, 1987) and each of the HPVs used in this study also encodes a similar protein (Bubb and Schlegel, 1988;Halbert and Galloway, 1988).…”

Section: Discussionmentioning

confidence: 99%

Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.

et al. 1988

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Keratinocytes electroporated with human papillomavirus (HPV) 11, 16 and 18) exhibited an increased cellular proliferation which was quantitated as microcolony and macrocolony formation. However, only macrocolonies induced by HPV-16 or HPV-18 DNA (the two viral types most commonly found in human cervical carcinomas) gave rise to proliferating, poorly-stratified colonies when grown in the presence of serum and calcium. Hydrocortisone increased the frequency of these differentiation-resistant colonies, and studies showed that they were immortalized, contained one copy of viral DNA per cell, expressed three discrete species of viral RNA and synthesized the viral E7 protein. HPV-induced cellular proliferation and altered differentiation are therefore separable events and may represent the activity of different viral genes.

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Section: Discussionmentioning

confidence: 99%

Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.

et al. 1988

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“…Our The major transforming proteins encoded by BPV-1 are E5 and E6. Each of these proteins is sufficient to induce transformation of murine C127 cells (11)(12)(13)(14)(15) . Although no independent oncogenic activity has been detected for BPV-1 E7, it was shown to be required for efficient transformation of C127 by BPV-1 (16).…”

mentioning

confidence: 99%

Activation of c-Myc Contributes to Bovine Papillomavirus Type 1 E7-induced Cell Proliferation

Fan¹,

Liu²,

Chen

2003

Journal of Biological Chemistry

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Inactivation of the tumor suppressor pRB by the human papillomavirus (HPV) oncoprotein E7 is a mechanism by which HPV promotes cell growth. The bovine papillomavirus type 1 (BPV-1) E7 does not bind pRB efficiently yet is required for full transformation of murine cells by BPV-1. In the present study, we investigated the mechanism of BPV-1 E7-induced cell proliferation. Our The major transforming proteins encoded by BPV-1 are E5 and E6. Each of these proteins is sufficient to induce transformation of murine C127 cells (11)(12)(13)(14)(15) . Although no independent oncogenic activity has been detected for BPV-1 E7, it was shown to be required for efficient transformation of C127 by BPV-1 (16). It was suggested that the transforming capability of BPV-1 E7 was repressed by other viral genes in the context of BPV-1 genome (17). We have recently shown that expression of BPV-1 E7 sensitizes cells to tumor necrosis factor-␣-induced apoptosis in the absence of Rb (18). In addition, conflicting data have been published on the role of BPV-1 E7 in BPV-1 genome copy number regulation (Ref. 19 and references therein).With the exception of the Cys-X-X-Cys motifs, the E7 proteins of the BPV-1 and the HPVs are quite different in their amino acid composition (Ͻ20% identity). BPV-1 E7 lacks the sequence motif (LXCXE) present in the HPV E7 proteins, which is critical for efficient binding to the Rb family proteins (20,21). However, the sequences in the C-terminal half of E7 proteins are well conserved between BPV-1 and HPVs. A low affinity pRB-binding site has been identified from the C terminus of . We have demonstrated a low affinity association of BPV-1 E7 protein with pRB but not p107 (18).In this study, we investigated the function and mechanism of BPV-1 E7 in cell proliferation. Our results indicate that BPV-1 E7 can stimulate cells to enter S phase in the absence of Rb.

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“…In these assays, open reading frames (ORFs) E5 and E6 have been identified as the major BPV1 transforming genes (4)(5)(6)(7)(8)(9). The 44-amino acid ORF E5 protein is required for efficient focus formation in the established line of mouse C127 cells (4,(10)(11)(12).…”

mentioning

confidence: 99%

Efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a bovine papillomavirus/simian virus 40 recombinant virus.

Settleman

DiMaio²

1988

Proc. Natl. Acad. Sci. U.S.A.

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To efficiently introduce bovine papillomavirus type 1 genes into cultured cells, we constructed a hybrid viral genome in which the simian virus 40 early region is replaced with a segment of the bovine papillomavirus type 1 transforming region. High-titer stocks of simian virus 40 virions containing the recombinant genome were produced in monkey cells that express simian virus 40 large tumor antigen. Cells infected with this virus efficiently expressed the bovine papillomavirus type 1 E2 and E5 genes. Expression of the E2 gene caused transactivation of genes linked to the bovine papillomavirus type 1 control region, resulting in up to a 1000-fold induction. At high multiplicity of infection of a cell line containing an integrated reporter gene, most cells were infected and responded to transactivation. Within 48 hr of infection with wild-type virus but not with an open reading frame ES mutant, mouse C127 cells displayed dramatic changes in morphology and growth characteristics similar to those seen in tumorigenic transformation. This system can be used to determine the acute cellular response to introduction of bovine papillomavirus type 1 transforming and regulatory genes; it can also be used to induce foreign genes stably incorporated into cultured mammalian cells.Bovine papillomavirus type 1 (BPV1) and other papillomaviruses can induce tumorigenic transformation of established rodent cells growing in culture (1, 2). Cell transformation by the papillomaviruses is a topic of considerable interest because of the strong association between human papillomavirus infection and some human squamous cell carcinomas, but little is known about the molecular mechanisms of papillomavirus transformation. This deficiency is due in large part to the lack of a cell culture system that allows papillomavirus propagation. Moreover, it is cumbersome to isolate wild-type virus from cow warts, and constructed viral mutants cannot be packaged into virus particles.Therefore, genetic analysis of transformation by these viruses has been largely restricted to determining the activity of transfected viral genes and mutants in stable transformation assays (3). In these assays, open reading frames (ORFs) E5 and E6 have been identified as the major BPV1 transforming genes (4-9). The 44-amino acid ORF E5 protein is required for efficient focus formation in the established line of mouse C127 cells (4,(10)(11)(12). The efficiency of transformation is also influenced by expression of ORF E2. The full-length E2 protein transactivates promoters linked to the BPV1 long control region (LCR), whereas separate proteins encoded by the 3' end of ORF E2 antagonize transactivation (5,6,(13)(14)(15)(16)(17)(18) inserted in place of the HindIII (nt 5171)-to-Bcl I (nt 2770) large tumor (T) antigen-coding fragment of SV40 DNA. These viral sequences are cloned into pBR322 at the unique EcoRI site in the SV40 late region. The HindIl, BamHI, and Bcl I sites at the junctions of the DNA fragments were lost, and a Xho I linker was inserted at the junction up...

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Genetic analysis of the 3′ early region transformation and replication functions of bovine papillomavirus type 1

Cited by 101 publications

References 16 publications

Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.

Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma.

Activation of c-Myc Contributes to Bovine Papillomavirus Type 1 E7-induced Cell Proliferation

Efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a bovine papillomavirus/simian virus 40 recombinant virus.

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