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Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein

Vogt, M, Butz, K, Dymalla, S, Semzow, J, Hoppe-Seyler, F·2006·Oncogene
DOI 10.1038/sj.onc.1209429
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Abstract

Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer in humans. The antiapoptotic viral E6 gene has been identified as a key factor for maintaining the viability of HPV-positive cancer cells. Although E6 has the potential to modulate many apoptosis regulators, the crucial apoptotic pathway blocked by endogenous E6 in cervical cancer cells remained unknown. Using RNA interference (RNAi), here, we show that targeted inhibition of E6 expression in cervical cancer cells leads to the transcriptional stimulation of the PUMA promoter, in a p53-dependent manner. This is linked to the activation and translocation of Bax to the mitochondrial membrane, cytochrome c release into the cytosol, and activation of caspase-3, in a PUMA-dependent manner. Moreover, inhibition of Bax expression by RNAi efficiently reverts the apoptotic phenotype, which results from inhibition of E6 expression. Thus, interference with the p53/PUMA/Bax cascade is crucial for the antiapoptotic function of the viral E6 oncogene in HPV-positive cancer cells.

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Metadata

Authors
Vogt, M., Butz, K., Dymalla, S., Semzow, J., & Hoppe-Seyler, F.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2006-02-06
Volume
25
Issue
29
Pages
4009-4015
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/sj.onc.1209429
Cited by
54
References
0
Language
en
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CoChat. (2026). Citation check: Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein. https://app.cochat.ai/papers/10.1038/sj.onc.1209429
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Vogt, M., Butz, K., Dymalla, S., Semzow, J., & Hoppe-Seyler, F. (2006). Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein. Oncogene. https://doi.org/10.1038/sj.onc.1209429