The papillomavirus E6 proteins

Rapp, Lisa; Chen, Jason J.

doi:10.1016/s0304-419x(98)00009-2

Cited by 64 publications

(74 citation statements)

References 167 publications

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“…These data allowed for the creation of an algorithm to search and identify the PBS sequences within the paxillin LD binding partners PKL, ILK, and actopaxin and other potential candidates (23, 183,184,274,278). The general utility of LD-PBS associations has emerged with the discovery of an interaction between gelsolin and PYK2 (294) as well as between the papillomavirus E6 protein and the ubiquitin ligase E6-AP (14, 47), the Rap-GAP E6TP1(67), and the Ca 2ϩ -binding protein ERC-55/ E6BP (38), in addition to paxillin (211).…”

Section: A Paxillin Ld Motifsmentioning

confidence: 99%

Paxillin: Adapting to Change

Brown¹,

Turner²

2004

Physiological Reviews

551

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Molecular scaffold or adaptor proteins facilitate precise spatiotemporal regulation and integration of multiple signaling pathways to effect the optimal cellular response to changes in the immediate environment. Paxillin is a multidomain adaptor that recruits both structural and signaling molecules to focal adhesions, sites of integrin engagement with the extracellular matrix, where it performs a critical role in transducing adhesion and growth factor signals to elicit changes in cell migration and gene expression.

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Section: A Paxillin Ld Motifsmentioning

confidence: 99%

Paxillin: Adapting to Change

Brown¹,

Turner²

2004

Physiological Reviews

551

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“…35 To further evaluate a possible role of p53 in TNF-induced apoptosis, the effect of TNF on p53 accumulation was examined in A2780 and A2780/E6 cells. As shown in Figure 6a, 24 hr treatment with rHuTNF (1,000 U/ml) induced an increase in the level of p53 in A2780 cells but did not affect its level in A2780/E6 cells.…”

Section: Sensitization By Hpv-16 E6 Is P53-independent and Cell Cyclementioning

confidence: 99%

Human papillomavirus type 16 E6‐enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line

Vikhanskaya¹,

Falugi²,

Valente³

et al. 2001

Intl Journal of Cancer

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In our study, we show that expression of HPV-16 E6 sensitizes TNF-induced cytotoxicity of human ovarian cancer cell line A2780. This effect is not related to a different number of TNF receptors present on cell membrane. The major induction of massive apoptosis induced by TNF is not p53-and p21waf-1 -dependent but it is principally related to NF-B inhibition in A2780/E6 cells. Consistently to NF-B inhibition a rapidly release of cytochrome c and severe induction of DNA fragmentation are seen in A2780/E6 cells. Also in human colon cancer cell line HCT-116/E6 the expression of HPV-16 E6 enhances TNF-cytotoxicity. This effect is not present in the HCT-116/mu-p53 clone (transfected with a dominant-negative mutated p53 transgene). Thus, taken together all these observations suggest that HPV-16 E6 sensitizes A2780 and HCT-116 cells to TNF; this effect is not p53-dependent, but it is essentially mediated through an inhibition in activating NF-B activities.

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“…HPV E7 is capable of binding and inactivating the retinoblastoma tumor suppressor protein and retinoblastoma homologs (3) as well as several other cellular targets (4). Although the best known function of HPV E6 is the targeting and ubiquitin-dependent degradation of the p53 tumor suppressor protein (5-7), E6 also binds to additional cellular proteins and has functions that are independent of p53 degradation (8). The growing list of E6 target proteins includes E6-BP (9), paxillin (10), hDIg (the human homologue of the Drosophila disc large tumor suppressor protein) (11,12), Mcm7 (minichromosome maintenance protein 7) (13,14), IRF-3 (IFN regulatory factor 3) (15), Myc (16,17), Bak (Bcl-2-homologous antagonist/killer) (18,19), E6TP-1 (E6-targeting protein 1) (20,21), CREB-binding protein/p300 (22,23), Tyk2 (protein-tyrosine kinase 2) (24), hScrib (the human homologue of the Drosophila Scribble (Vartul) tumor suppressor protein) (25), PKN (a novel protein kinase with a catalytic domain homologous to that of protein kinase C) (26), MUPP1 (multi-PDZ domain protein 1) (27), MAGI-1 (membrane-associated guanylate kinase protein) (28), Gps2 (G-protein pathway suppressor 2) (29), ADA3 (30,31), and tuberin (32).…”

mentioning

confidence: 99%

The E6AP Ubiquitin Ligase Is Required for Transactivation of the hTERT Promoter by the Human Papillomavirus E6 Oncoprotein

Yuan

et al. 2005

Journal of Biological Chemistry

103

111

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Most human cancer cells display increased telomerase activity that appears to be critical for continued cell proliferation and tumor formation. The E6 protein of malignancy-associated human papillomaviruses increases cellular telomerase in primary human keratinocytes at least partly via transcriptional activation of the telomerase catalytic subunit, hTERT. In the present study, we investigated whether E6AP, a ubiquitin ligase well known for binding and mediating some of the activities of the E6 oncoprotein, participated in the transactivation of the hTERT promoter. Our results demonstrate that E6 mutants that fail to bind E6AP are also defective for increasing telomerase activity and transactivating the hTERT promoter. More importantly, E6AP knock-out mouse cells and small interfering RNA techniques demonstrated that E6AP was required for hTERT promoter transactivation in both mouse and human cells. Neither E6 nor E6AP bound to the hTERT promoter or activated the promoter in the absence of the partner protein. With all transactivation-competent E6 proteins, induction of the hTERT promoter was dependent upon E box elements in the core promoter. It appears, therefore, that E6-mediated activation of the hTERT promoter requires a complex of E6-E6AP to engage the hTERT promoter and that activation is dependent upon Myc binding sites in the promoter. The recruitment of a cellular ubiquitin ligase to the hTERT promoter during E6-mediated transcriptional activation suggests a role for the local ubiquitination (and potential degradation) of promoter-associated regulatory proteins, including the Myc protein.

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The papillomavirus E6 proteins

Cited by 64 publications

References 167 publications

Paxillin: Adapting to Change

Paxillin: Adapting to Change

Human papillomavirus type 16 E6‐enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line

The E6AP Ubiquitin Ligase Is Required for Transactivation of the hTERT Promoter by the Human Papillomavirus E6 Oncoprotein

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