The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product

Dyson, Nicholas J.; Howley, Peter; Münger, Karl; Harlow, Ed

doi:10.1126/science.2537532

Cited by 2,772 publications

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References 45 publications

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“…A number of cellular targets of the viral oncogenes of anogenital viruses have been identi®ed. These include the Rb and p53 proteins which are targeted by the viral E7 and E6 genes respectively (Dyson et al, 1989;Werness et al, 1990). The p53 tumour suppressor protein plays a pivotal role in cellular responses to stress factors such as DNA damage or hypoxia, principally through an induction of either cell cycle arrest or apoptosis (reviewed in Amundsen et al, 1998).…”

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confidence: 99%

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

2000

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In addition to their role in anogenital cancer, human papillomaviruses (HPVs) are also involved in the development of a range of cutaneous lesions. HPV types 5 and 8 are associated with the development of skin cancers in individuals with Epidermodysplasia verruciformis (EV). A broad spectrum of HPV types are also commonly found in non-melanoma skin cancers in immunocompromised individuals, such as organ transplant recipients. The skin cancers in EV and immunocompromised patients occur predominantly at body sites exposed to ultra violet (UV) radiation, pointing to a key role for UV in their development. Here we show that the E6 protein from a range of cutaneous HPV types e ectively inhibits apoptosis in response to UV damage. This occurs in both p53 null and wild type cells and does not require p53 degradation. Oncogene (2000) 19, 592 ± 598.

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confidence: 99%

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

2000

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“…These viruses encode two oncogenes E6 and E7 that can transform keratinocytes by interacting with cell cycle regulators. E6 binds to and degrades the p53 regulatory protein, while E7 interacts with members of the pRb family (Dyson et al, 1989;Sche ner et al, 1990). However, expression of the viral oncogenes is not su cient for carcinogenic progression, which requires additional events, one of them being the integration of the viral DNA into the host cell genome.…”

Section: Introductionmentioning

confidence: 99%

Papillomavirus E2 induces p53-independent apoptosis in HeLa cells

et al. 1999

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We have previously shown that expression of the papillomavirus E2 protein in HeLa cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. In contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. In the present study, we conducted biochemical and genetic experiments in order to determine whether E2-induced apoptosis was independent of p53 induction. We showed that E2 did not alter the transcription of Bax, a known p53-activated cell death inducer. The time course of apoptotic cell death preceded p53 induction by several hours. Overexpression of the HPV18 E6 oncogene prevented E2-mediated p53 accumulation, but did not alter the rate of cell death. Finally, point mutants of the HPV18 E2 transactivation domain induced apoptosis, although they were unable to induce high p53 accumulation or cell cycle arrest. In addition, the results obtained with these mutants indicated that both transcriptional activation and replication functions of E2 were dispensable for the induction of cell death. These observations show that E2-induced apoptosis is an early event, independent of p53 accumulation and unrelated to downstream p53-dependent transcriptional events.

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“…The HPV16 E7 protein is able to induce focus formation and growth in soft agar in a variety of established rodent ®broblast lines and to co-operate with E6 to immortalize primary human keratinocytes (reviewed by Mansur and Androphy, 1993). These activities are in part explained by the ability of E7 to interact with and to induce destabilization of the so-called`pocket' proteins, pRb, p107 and p130 (Dyson et al, 1989;Davies et al, 1993;Hu et al, 1995;Boyer et al, 1996;. The pocket proteins are central regulators of cell cycle division.…”

Section: Introductionmentioning

confidence: 99%

Induction of S phase and apoptosis by the human papillomavirus type 16 E7 protein are separable events in immortalized rodent fibroblasts

et al. 2000

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The HPV16 E7 oncoprotein neutralizes several cell cycle checkpoints, favouring the entry of quiescent cells into S phase. This activity is mediated in part by association of E7 with the pocket proteins and consequent activation of E2F transcription factors. In addition, HPV16 E7 protein is able to promote apoptosis. In this study we demonstrate that the ability to induce apoptosis is a common property of E7s belonging to both benign and malignant HPV types. The E7-induced apoptosis is mediated by inactivation of pRb, whilst neutralization of the other two pRB-related proteins, p107 and 130, is not su cient to trigger apoptosis. Moreover, we show that certain point mutations in the conserved region 1 (CR1) of HPV16 E7 abolish the induction of apoptosis without altering the ability to stimulate S phase. Thus, these two E7-mediated cellular events, apoptosis and S phase entry, can be separated in immortalized rodent ®broblasts. Our ®ndings demonstrate that the E7-mediated pRb destabilization is not required for its ability to drive quiescent cells into S phase and to induce apoptosis. Finally, expression of E7 proteins in NIH3T3, which lack a functional p19 ARF , does not lead to p53 accumulation, indicating that the E7 impacts upon additional cellular pathways to promote apoptosis.

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The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product

Cited by 2,772 publications

References 45 publications

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

Papillomavirus E2 induces p53-independent apoptosis in HeLa cells

Induction of S phase and apoptosis by the human papillomavirus type 16 E7 protein are separable events in immortalized rodent fibroblasts

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