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 -
