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The HPV-16 E5 Protein Inhibits TRAIL- and FasL-Mediated Apoptosis in Human Keratinocyte Raft Cultures
Abstract
By using raft cultures of the polyclonal HaCaT cell lines stably transfected either with E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as reference, we investigated the effect of the human papillomavirus type 16 (HPV-16) E5 protein on apoptosis. In comparison to conventional monolayer cultures this model system allows analysis of apoptosis under more tissue-like conditions by mimicking the stratified organization of a normal surface epithelium. Apoptosis was triggered either by FasL or TRAIL. Execution of the death program was checked at early and late stages by monitoring procaspase-3 cleavage and DNA fragmentation, respectively. Rafts of E5-expressing keratinocytes were completely protected from apoptosis and showed a background of apoptotic cells as low as the untreated cultures. In contrast, the HaCaT/pMSG cultures revealed a dramatic increase in apoptotic cells upon ligand treatment throughout the epithelial compartment. We conclude that the presence of the HPV-16 E5 protein in our tissue-like model prevents FasL- or TRAIL-mediated apoptosis.
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“the expression of HPV-16 E5 prevents FasL- or TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by downregulating the expression of Fas receptors and abrogating the recruitment of the Fas-associated protein with death domain (FADD) to form the death-induced signalling complex (DISC) in raft cultures of HaCaT cells stably expressing HPV-16 E5 [197]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [197]
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Cites
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Identification and characterization of a new member of the TNF family that induces apoptosis
Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., et al. (1995) · Immunity · doi:10.1016/1074-7613(95)90057-8 · Cited by 2,900
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Cited by
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Metadata
- Authors
- Kabsch, K., Mossadegh, N., Kohl, A., Komposch, G., Schenkel, J., Alonso, A., & Tomakidi, P.
- Venue
- Intervirology
- Publisher
- S. Karger AG
- Published
- 2004
- Volume
- 47
- Issue
- 1
- Pages
- 48-56
- ISSN
- 0300-5526
- 1423-0100
- Cited by
- 58
- References
- 2
- Language
- en
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- Kabsch, K., Mossadegh, N., Kohl, A., Komposch, G., Schenkel, J., Alonso, A., & Tomakidi, P. (2004). The HPV-16 E5 Protein Inhibits TRAIL- and FasL-Mediated Apoptosis in Human Keratinocyte Raft Cultures. Intervirology. https://doi.org/10.1159/000076642
