Involvement of human papillomavirus type 8 genes E6 and E7 in transformation and replication

Iftner, Thomas; Bierfelder, S; Csapo, Z.; Pfister, Herbert

doi:10.1128/jvi.62.10.3655-3661.1988

Cited by 77 publications

(30 citation statements)

References 37 publications

(34 reference statements)

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“…It is conceivable therefore, that these proteins may have a different cellular target. This possibility is consistent with data from in vitro assays indicating that the E6 open reading frame (ORF) of HPVs 5 and 8 encodes a major transforming activity (Iftner et al, 1988). NMSC is also a major cause of morbidity in renal transplant recipients (RTRs) and other patients subjected to immunosuppressive therapy.…”

Section: Introductionsupporting

confidence: 86%

The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence

et al. 1999

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An aetiological role has been proposed for human papillomavirus (HPV) in skin carcinogenesis within the immunosuppressed patient population. To examine this possibility, we have focused on an HPV type that, to date, has been identified only in the cutaneous lesions of renal transplant recipients despite a high degree of sequence homology with other HPVs commonly found in warts in the general population. We report that the non-coding region of this virus, HPV type 77, contains a consensus binding site for the tumour suppressor protein p53, and we show by gel-retardation analysis that this sequence does indeed bind p53. Furthermore, using reporter gene assays, we demonstrate that HPV77 promoter activity is stimulated by UV radiation and that this response is mediated through the p53 binding site. This is the first report of a p53-dependent positive response element within a viral genome. Our results suggest a possible novel mechanism by which specific types of HPV might act as cofactors with UV radiation in cutaneous transformation.

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Section: Introductionsupporting

confidence: 86%

The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence

et al. 1999

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“…Using monolayer cultures, the E6 gene of HPV 8 shows transforming properties in rodent fibroblast lines (C127, Rat 1), whereas HPV 8 E7 is involved in the replication of the viral DNA [116]. HPV 47 E6 is required and sufficient for the transformation of the rat fibroblastic cell line (3Y1) [117].…”

Section: Monolayermentioning

confidence: 99%

“…The oncogenic potential of HPV types 5, 8, and 47 is higher than those of HPV types 14, 20, 21, and 25. The E7 genes of HPV 8 and HPV 47 fail to induce morphological transformation in rodent fibroblast lines suggesting that E6 rather than E7 is correlated to malignant conversion [116,119]. However, HPV 8 E7 is able to transform rodent cells concertedly with the activated Ha-ras oncogene [120].…”

Section: Monolayermentioning

confidence: 99%

Human Papillomaviruses and Non‐Melanoma Skin Cancer: Basic Virology and Clinical Manifestations

2007

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Human papillomaviruses (HPV) infect cutaneous and mucosal epithelia and induce benign and malignant lesions. Non-melanoma skin cancer (NMSC), encompassing basal cell carcinoma and squamous cell carcinoma (SCC), is the most frequent cancer in the Caucasian population, and the incidence has increased dramatically worldwide. Ultraviolet (UV) radiation is a major risk factor for NMSC, and cutaneous HPV is also considered to play an active role during the pathogenesis of these cancers. The first evidence for the involvement of HPV in NMSC was reported in patients with Epidermodysplasia verruciformis (EV). HPV types detected in skin tumours of these patients are referred to as EV/cutaneous HPV types belonging to the beta- and gamma-papillomaviruses (PV). Epidemiological studies have shown a higher risk of several EV/cutaneous HPV types for NMSC. Furthermore, in vitro and animal models show transforming properties of some PV types. The anti-apoptotic activities, and the delay of DNA repair mechanism caused by some EV/cutaneous HPV E6 proteins in response to UV-induced mutations, may lead to the persistence of DNA-damaged keratinocytes. Thus, specific EV/cutaneous HPV types as co-factors in association with UV-radiation and the immune system seem to be involved in the early pathogenesis of cutaneous SCC.

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“…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

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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.

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Involvement of human papillomavirus type 8 genes E6 and E7 in transformation and replication

Cited by 77 publications

References 37 publications

The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence

The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence

Human Papillomaviruses and Non‐Melanoma Skin Cancer: Basic Virology and Clinical Manifestations

Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein.

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