Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines.

Androphy, Elliot J.; Hubbert, Nancy L.; Schiller, John T.; Lowy, Douglas R.

doi:10.1002/j.1460-2075.1987.tb04849.x

Cited by 221 publications

(148 citation statements)

References 15 publications

(23 reference statements)

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“…Indeed, 99.7% of invasive cervical carcinomas worldwide contain and express DNA from HPV (Walboomers et al, 1999;Herrington, 1999), with HPV-16 and 18 being the types most frequently found in these tumors. The early viral proteins E6 and E7 are continually expressed in HPV-associated cervical cancer tissues and cell lines derived from cervical tumors (Hawley-Nelson et al, 1989;Androphy et al, 1987;Choo et al, 1987;Schwarz et al, 1985). These two oncoproteins can physically interact with and functionally disrupt two major cell cycle regulatory proteins, namely p53 and the retinoblastoma gene product (pRb), respectively (Werness et al, 1990;Dyson et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

et al. 2000

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Section: Introductionmentioning

confidence: 99%

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

et al. 2000

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“…Of this subset some HPV types, such as 6 and 11, are found associated with benign lesions whereas other types, such as 16 and 18, are commonly associated with lesions that can progress to high-grade cervical intraepithelial neoplasia and ultimately to cervical cancer (zur Hausen and Schneider, 1987). The early viral proteins E6 and E7 are continually expressed in cell lines derived from cervical tumours (Smotkin and Wettstein, 1986;Androphy et al, 1987;Banks et al, 1987). They interact with key cellular tumour suppressors; E7 with pRb (Dyson et al, 1989) and E6 with p53 , and can cooperate to immortalise primary human keratinocytes (Barbosa and Schlegel, 1989;Hawley-Nelson et al, 1989;Munger et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth

1997

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The E6 proteins originating from the tumour-associated Human Papillomavirus (HPV) types 16 and 18 have been shown to bind to and target the tumour suppressor protein, p53, for ubiquitin-mediated degradation. However, in cell lines derived from cervical neoplasias, the predominant early region transcripts are spliced and encode truncated forms of E6, termed E6*. We report here that HPV-18 E6* protein will interact both with the full-length E6 proteins from HPV-16 and HPV-18 and also with E6-AP, and subsequently blocks the association of full length E6 protein with p53. We also show that, as a result of this block, E6* can inhibit E6-mediated degradation of p53 both in vitro and in vivo. The biological consequences of this are increased transcriptional activity on p53-responsive promoters and an inhibition of cell growth in cells transfected with E6*. This is the ®rst report of a potential biological function for this polypeptide and may represent a means by which HPV is able to modulate the activity of the full-length E6 protein with respect to p53 during viral infection.

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“…These viruses encode two principal oncoproteins, E6 and E7, both of which are continually expressed in cervical tumours and cell lines derived therefrom (Smotkin and Wettstein, 1986;Androphy et al, 1987;Banks et al, 1987). Inhibition of the expression of either protein results in a cessation of transformed cell growth (von Knebel Doeberitz et al, 1988;Crook et al, 1989;Storey et al, 1994); hence both proteins represent ideal therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines

Mantovani

Banks

1999

Oncogene

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The E6 proteins derived from tumour associated papillomavirus types target the cellular tumour suppressor protein p53 for ubiquitin mediated degradation. In cell lines derived from cervical tumours the p53 protein is present in very low amounts, but it can be activated by appropriate DNA damaging agents, indicating that functional p53 is present within these lines. Recent studies have also shown that di erent polymorphic forms of the p53 protein are di erentially susceptible to E6 mediated degradation. Therefore we have been interested in analysing the e ects of di erent HPV E6 proteins upon p53 levels in a variety of cervical tumour derived cell lines. We show that inhibition of E6 mediated degradation of p53 frequently results in increased levels of p53 expression. However, there are notable exceptions to this where increased p53 levels are only obtained following DNA damage and proteasome inhibition. We also show in E6 expressing cells, that as well as p53 being targeted for degradation, the localization of p53 to the nucleus is also inhibited, consistent with previous observations which indicate that degradation of p53 is not essential for E6 mediated inhibition of p53 function. These results have important implications for any potential therapies which might aim to block E6 mediated degradation of p53.

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Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines.

Abstract: Human cervical carcinoma cell lines that harbor human papillomavirus (HPV)

Cited by 221 publications

References 15 publications

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth

Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines

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