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

Dorte Wissing Kaznelson; Silas Bruun; Astrid Monrad; Simon Gjerløv; Jesper Birk; Carsten Röpke; Bodil Norrild

doi:10.1016/j.virol.2003.12.018

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

Dorte Wissing Kaznelson, Silas Bruun, Astrid Monrad, Simon Gjerløv, Jesper Birk, Carsten Röpke, Bodil Norrild

31 Citations (Scopus)

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.

Original language	English
Journal	Virology
Volume	320
Issue number	2
Pages (from-to)	301-12
Number of pages	11
ISSN	0042-6822
DOIs	https://doi.org/10.1016/j.virol.2003.12.018
Publication status	Published - 2004

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@article{00b34310e7c311ddbf70000ea68e967b,

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

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.",

author = "Kaznelson, {Dorte Wissing} and Silas Bruun and Astrid Monrad and Simon Gjerl{\o}v and Jesper Birk and Carsten R{\"o}pke and Bodil Norrild",

note = "Keywords: Apoptosis; Cathepsin B; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Enzyme Activation; Humans; Oncogene Proteins, Viral; Papillomaviridae; Transgenes",

year = "2004",

doi = "10.1016/j.virol.2003.12.018",

language = "English",

volume = "320",

pages = "301--12",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press",

number = "2",

}

TY - JOUR

T1 - Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

AU - Kaznelson, Dorte Wissing

AU - Bruun, Silas

AU - Monrad, Astrid

AU - Gjerløv, Simon

AU - Birk, Jesper

AU - Röpke, Carsten

AU - Norrild, Bodil

N1 - Keywords: Apoptosis; Cathepsin B; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Enzyme Activation; Humans; Oncogene Proteins, Viral; Papillomaviridae; Transgenes

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1016/j.virol.2003.12.018

DO - 10.1016/j.virol.2003.12.018

M3 - Journal article

C2 - 15016552

SN - 0042-6822

VL - 320

SP - 301

EP - 312

JO - Virology

JF - Virology

IS - 2

ER -

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

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