Cell cycle-dependent disruption of E2F-p107 complexes by human papillomavirus type 16 E7

Zerfass, K; Levy, Laura M.; Cremonesi, Caterina; Ciccolini, Francesca; Jansen‐Dürr, Pidder; Crawford, L. V.; Ralston, Robert R.; Tommasino, Massimo

doi:10.1099/0022-1317-76-7-1815

Cited by 27 publications

(13 citation statements)

References 28 publications

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“…As yet we do not have an explanation for this e ect, however, a similar, but not identical, situation was observed with papillomavirus E7 protein which was found to dissociate p107 containing complexes only if they did not at the same time carry cyclin A, i.e. E7 dissociated p107 complexes in G 1 but not in S phase (Zerfass et al, 1994). The recent observation (Ikeda and Nevins, 1993) that E1A protein may have two separate functions in its activity towards pocket proteins, one being the capacity to bind the protein, the other one the dissociation of complexes, might be relevant in this regard.…”

Section: Mrc5mentioning

confidence: 69%

Polyomavirus large T antigen-dependent DNA amplification

et al. 1997

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DNA ampli®cation is a readily measurable indicator for genome destabilization. Contrary to normal senescing cells, those of most immortal or transformed cell lines are karyotypically unstable and permissive for ampli®ca-tion. Permissivity for ampli®cation can be generated by gene products of several DNA tumor viruses whereby their interaction with the tumorsuppressor protein p53 is important. p53 is the major protein involved in check point control of DNA damage. Polyomavirus large T antigen is also involved in immortalization and transformation of cells but it does not interact with p53. We, therefore, examined whether this protein could still make the non-permissive cell line REF52 permissive for gene ampli®cation. To this end REF52 cell lines were constructed which conditionally expressed the wild type polyomavirus large T antigen or a mutant form unable to bind the retinoblastoma protein. Using the inhibitor of de novo pyrimidine biosynthesis, phosphonoacetyl-L-aspartate (PALA), as selective agent we found that PALA resistant cells arise with a frequency of about 5610 75 and that the interaction of polyomavirus large T protein with the retinoblastoma protein or another related pocket protein is important for this to occur. PALA resistant cells have an increased number of chromosomes and dicentric chromosomes which are considered as starting point for DNA structures characteristic for ampli®ed DNA. Such structures were indeed found with the help of uorescence in situ hybridization. PALA resistant cells appear normal with respect to p53. Our data indicate that PALA induces a G 1 block which can be partially overcome by polyomavirus large T protein by its interaction with E2F-pocket protein complexes providing further evidence that these complexes are downstream targets of p53.

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Section: Mrc5mentioning

confidence: 69%

Polyomavirus large T antigen-dependent DNA amplification

et al. 1997

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“…While Harrington et al showed that Rb, but not p107 and p130, was essential for G 1 control in DNA-damaged mouse embryo fibroblasts (28), others have provided evidence that p107 and/or p130 function in murine cell cycle control following DNA damage (59,63). The mechanism by which E7 inactivates p107 and p130 is not clear and may differ according to cell type (1,4,40,68). In agreement with Jones et al (40), we find that E7 reduces p107 and p130 levels, and we extended these findings to show that the same regions of E7 are required for reducing Rb, p107, and p130 levels.…”

Section: Discussionmentioning

confidence: 99%

Destabilization of the Retinoblastoma Tumor Suppressor by Human Papillomavirus Type 16 E7 Is Not Sufficient To Overcome Cell Cycle Arrest in Human Keratinocytes

Helt

Galloway

2001

J Virol

140

162

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The E7 oncoprotein of human papillomavirus type 16 promotes cell proliferation in the presence of antiproliferative signals. Mutagenesis of E7 has revealed that this activity requires three regions, conserved regions 1 and 2 and a C-terminal zinc finger. Binding to the retinoblastoma tumor repressor (Rb) through an LxCxE motif in conserved region 2 is necessary, but not sufficient, for E7 to induce proliferation. We tested the hypothesis that binding to Rb is not sufficient because conserved region 1 and/or the C terminus are required for E7 to functionally inactivate Rb and thus induce proliferation. One mechanism proposed for how E7 inactivates Rb is by blocking Rb-E2F binding. Either conserved region 1 or the C terminus was necessary, in combination with the LxCxE motif, for E7 to block Rb-E2F binding in vitro. While all full-length E7 proteins with mutations outside of the LxCxE motif inhibited Rb-E2F binding, some failed to abrogate cell cycle arrest, demonstrating that blocking Rb-E2F binding is not sufficient for abrogating antiproliferative signals. Another mechanism proposed for how E7 inactivates Rb is by promoting the destabilization of Rb protein. Mutations in conserved region 1 or the LxCxE motif prevented E7 from reducing the half-life of Rb. Though no specific C-terminal residues of E7 were essential for destabilizing Rb, a novel class of mutations that uncouple the destabilization of Rb from the deregulation of keratinocyte proliferation was discovered. Destabilization of Rb correlated with the abrogation of Rb-induced quiescence but was not sufficient for overriding DNA damageinduced cell cycle arrest or for increasing keratinocyte life span. Finally, the same regions of E7 required for destabilizing Rb were required for reducing p107 and p130 levels. Together, these results suggest that inactivation of all three Rb family members is not sufficient to deregulate keratinocyte cell cycle control.

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“…In addition, it binds to the cdk inhibitor proteins p21/WAF1 and p27/Kip1, blocking their binding to cyclins and, in the case of p21, PCNA and disrupting normal cell cycle control [70]. Similar to Rb, the Rb-related protein p107 is also bound by E7, leading to release of E2F transcription factors from p107 in the G1 phase [69]. Furthermore, E7 binds to Mi2β, a member of the histone deacetylase complex which influences the histone-DNA interaction and the access of transcription factors [3], probably leading to deregulation of genes that govern the cell cycle.…”

Section: High-grade Squamous Intraepithelial Lesionsmentioning

confidence: 99%

Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications

Milde‐Langosch¹,

Riethdorf²,

Löning³

2000

Virchows Archiv

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Human papillomaviruses (HPVs) are the major aetiological agents of cervical carcinoma. In this review, epidemiological and molecular data are combined to present a model for HPV-induced cervical carcinogenesis. The impact of current knowledge regarding diagnostic and therapeutic approaches is shown, i.e. the use of HPV tests in cervical cancer screening, in the management of atypical smears of uncertain diagnosis and in smears indicative of mild dysplasias, as well as in follow-up examinations during and after therapy. In addition, the value of the two most frequently used HPV detection systems, polymerase-chain reaction (PCR) and hybrid capture (HC) analysis, is discussed.

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Cell cycle-dependent disruption of E2F-p107 complexes by human papillomavirus type 16 E7

Cited by 27 publications

References 28 publications

Polyomavirus large T antigen-dependent DNA amplification

Polyomavirus large T antigen-dependent DNA amplification

Destabilization of the Retinoblastoma Tumor Suppressor by Human Papillomavirus Type 16 E7 Is Not Sufficient To Overcome Cell Cycle Arrest in Human Keratinocytes

Association of human papillomavirus infection with carcinoma of the cervix uteri and its precursor lesions: theoretical and practical implications

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