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Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

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Authors:
  • Kaznelson, Dorte Wissing ;
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    unknown
  • Bruun, Silas ;
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    Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet
  • Monrad, Astrid ;
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    Hansen Group, BRIC Research Groups, BRIC, Københavns Universitet
  • Gjerløv, Simon ;
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    unknown
  • Birk, Jesper ;
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    Orcid logo0000-0001-9775-4789
    Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
  • Röpke, Carsten ;
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    unknown
  • Norrild, Bodil
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    Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
DOI:
10.1016/j.virol.2003.12.018
Abstract:
Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induction of cell death. We have used the osteosarcoma cell line U2OS cells provided with E7 and the cdk2 inhibitor p21 (cip1/waf1) under inducible control, as a model system for the analysis of E7-mediated apoptosis. Our data shows that simultaneous expression of E7 and p21 proteins induces cell death, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge, this is the first time a role for cathepsin B is reported in HPV-induced apoptotic signalling.
Type:
Journal article
Language:
English
Published in:
Virology, 2004, Vol 320, Issue 2, p. 301-12
Main Research Area:
Science/technology
Publication Status:
Published
Review type:
Peer Review
Submission year:
2004
Scientific Level:
Scientific
ID:
39035046

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