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The HPV E7 oncoprotein inhibits tumor necrosis factor α-mediated apoptosis in normal human fibroblasts

Thompson, David Alan, Zacny, Valerie, Belinsky, Glenn Scott, Classon, Marie, Jones, Dana Leanne, Schlegel, Robert, Münger, Karl·2001·Oncogene
DOI 10.1038/sj.onc.1204483
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Abstract

Tumor necrosis factor-alpha (TNF) is a cytokine that induces programmed cell death, apoptosis, in a number of cell types and is employed by cytotoxic T cells to eliminate virus infected cells. Consequently, many viruses have acquired mechanisms to undermine these host cell defense mechanisms and cause resistance to TNF-mediated apoptosis. Here we show that normal human diploid fibroblasts that express the human papillomavirus type 16 E7 oncoprotein have a decreased propensity to undergo apoptosis in response to TNF treatment. The ability of E7 to undermine TNF-mediated apoptosis correlates with cellular transformation. While E7 does not generally subvert signaling by tumor necrosis factor receptor 1, pro-caspase 8 activation is decreased in E7-expressing cells. E7 also provides some protection from apoptosis caused by stimulation of the TNF receptor 1-related cytokine receptor Fas, where induction of apoptosis occurs much slower in this cell type. Hence, E7-expressing normal human fibroblasts exhibit a specific defect that obstructs cytokine-mediated activation of pro-caspase 8 and apoptosis.

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Crossref · 10.1038/sj.onc.1204483

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Cited by

Metadata

Authors
Thompson, D. A., Zacny, V., Belinsky, G. S., Classon, M., Jones, D. L., Schlegel, R., & Münger, K.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2001-06-21
Volume
20
Issue
28
Pages
3629-3640
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/sj.onc.1204483
Cited by
44
References
1
Language
en
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