The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells

Bedell, Mary A.; Jones, Katherine H.; Laimins, Laimonis A.

doi:10.1128/jvi.61.11.3635-3640.1987

Cited by 166 publications

(65 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another distinct group of HPVs which includes HPV-6 and HPV-is associated with benign anogenital lesions, such as condyloma accuminata, with little risk for malignant progression and these viruses are considered 'low risk' viruses. The difference between the high risk and low risk groups of HPVs is also manifested in in vitro transformation systems. Transfection of cloned HPV-16 or HPV-18 DNA leads to transformation of rodent cells (Yasumoto et al, 1986;Bedell et al, 1987;Kanda et al, 1987) and to immortalization of primary human cells (Durst et al, 1987;Pirisi et al, 1987;Schlegel et al, 1988), further supporting ©) Oxford University Press a causative role of these specific HPVs in carcinogenesis. In contrast, cloned DNAs of the low risk HPVs, such as HPV-6 or HPV-11, are either negative or only weakly transforming in the same assays.…”

Section: Introductionmentioning

confidence: 99%

Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.

et al. 1992

View full text Add to dashboard Cite

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 accelerated degradation of p53 in vitro via the ubiquitin-dependent proteolysis system. In this study we demonstrate that a fusion protein consisting of the N-terminal half of the HPV-16 E7 protein and the full length HPV-16 E6 protein promotes the in vitro degradation of the retinoblastoma protein.This indicates that the property of the HPV-16 E6 protein to stimulate the degradation of p53 can be targeted to other proteins. Unlike the HPV-16 or HPV-18 E6 protein, the E6 proteins of HPV-6 and 11 do not bind to p53 and consequently do not target p53 for degradation. Analogous E7 -E6 fusion proteins using the E6 proteins of HPV-6 and HPV-11, however, also have the ability to promote the degradation of the retinoblastoma protein, indicating that the property to target associated proteins for degradation is shared by the anogenital specific HPV E6 proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.

et al. 1992

View full text Add to dashboard Cite

show abstract

“…The 137 amino acid bovine papillomavirus (BPV) E6 protein induced morphologic transformation of rodent cells in vitro (Schiller et al, 1984;Androphy et al, 1985). HPV E6 genes were less efficient in the focus formation assay than their bovine counterpart; however, several in vitro models have confirmed the role of HPV E6 genes in transformation (Bedell et al, 1987;Iftner et al, 1988;Cerni et al, 1989;Hawley-Nelson et al, 1989;Munger et al, 1989;Watanabe et al, 1989;Hudson et al, 1990). Comparison of BPV E6 with human HPV E6 proteins reveals only moderate conservation of amino acids, most evident in the two pairs of cysteine repeats (Cys-x-x-Cys), postulated to mediate metal binding and the formation of a 'finger' conformation, and residues within the fingers (Cole and Danos, 1987).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein.

et al. 1990

View full text Add to dashboard Cite

The introduction of the bovine (BPV) or human papillomavirus E6 gene into susceptible cells can result in their transformation, but there are few clues to the mechanism of action of the E6 gene. The characteristic features of E6 proteins are their small size (approximately 150 amino acids) and the potential to form two large zinc fingers. To determine if E6 can function as a transcription factor, the BPV E6 gene was fused to the sequence specific DNA binding peptide encoded by the BPV E2 gene. This chimeric E6‐E2 protein trans‐activated promoters that incorporated E2 binding elements in both rodent cells and Saccharomyces cerevisiae. In the absence of E6‐E2 localization to the target promoter, trans‐activation did not occur. Alteration of the cysteine residues at the base of each finger abrogated the transcriptional activity of the E6‐E2 hybrids. These data demonstrated that the BPV E6 gene encodes a transcription activation domain and imply that a specific structure of the protein, most likely the zinc fingers, is critical for this function. Since these cysteine mutants are also transformation defective, E6 transcriptional functions may be required for its oncogenic activity.

show abstract

“…The corresponding viral proteins E6 and E7 can be detected in the malignant cells using mono-and polyclonal antibodies Banks et al, 1987;Seedorf et al, 1987;Smotkin and Wettstein, 1987). Obviously these viral genes encode for at least one transforming function, since the transfection of plasmids containing the E6/E7 ORFs of HPV 18 is sufficient to transform NIH-3T3 and Rat-I cells (Bedell et al, 1987). In addition, the role of HPV 18 E6 and E7 gene expression could be linked to the proliferative phenotype of C4-1 cervical cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

1988

View full text Add to dashboard Cite

The transcription of human papillomavirus type 18 (HPV 18) is selectively suppressed in non‐tumorigenic HeLa x fibroblast or HeLa x keratinocyte cell hybrids by 5‐azacytidine. In contrast, viral gene expression is not influenced by 5‐azacytidine in both tumorigenic hybrid segregants and in the parental HeLa cells. The suppression mechanism seems to operate at the level of initiation of transcription since nuclear run‐on experiments show the absence of elongated nascent viral RNA, whereas the transcription of cellular reference genes remains unaffected. Down‐regulation of HPV 18 mRNA correlates directly with cessation of cellular growth and can be abolished using the protein synthesis inhibitor cycloheximide. Furthermore human keratinocytes immortalized by HPV 16 but still retaining the non‐tumorigenic phenotype reveal the same inhibitory effect on viral transcription after treatment with 5‐azacytidine. These results support a model of a postulated intracellular control mechanism, directed against papillomavirus transcription, which can be induced by 5‐azacytidine and appears to correlate with the presence of specific chromosomes in non‐tumorigenic cells.

show abstract

The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells

Cited by 166 publications

References 28 publications

Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.

Targeted degradation of the retinoblastoma protein by human papillomavirus E7-E6 fusion proteins.

Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein.

Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-azacytidine.

Contact Info

Product

Resources

About