TY - JOUR
T1 - The human papillomavirus 16 E6 protein can either protect or further sensitize cells to TNF
T2 - Effect of dose
AU - Filippova, M.
AU - Brown-Bryan, T. A.
AU - Casiano, C. A.
AU - Duerksen-Hughes, P. J.
N1 - Funding Information:
This work was supported in part by NCI Grant 1 R01 CA-095461 (PDH) and NIAID Grant R29 AI-44088 (CAC) from the National Institutes of Health. In addition, we thank Dr. Eng Tan (Scripps Research Institute) for the Topo I antibody, Dr. Carl Ware (La Jolla Institute for Allergy and Immunology) for the plasmid encoding TNF R1 and Christine Molinaro (Loma Linda University) for her technical assistance.
PY - 2005/12
Y1 - 2005/12
N2 - High-risk strains of human papillomavirus, including HPV 16, cause human cervical carcinomas, due in part to the activity of their E6 oncogene. E6 interacts with a number of cellular proteins involved in host-initiated apoptotic responses. Paradoxically, literature reports show that E6 can both protect cells from and sensitize cells to tumor necrosis factor (TNF). To examine this apparent contradiction, E6 was transfected into U2OS cells and stable clones were treated with TNF. Intriguingly, clones with a high level of E6 expression displayed an increased sensitivity to TNF by undergoing apoptosis, while those with low expression were resistant. Furthermore, TNF treatment of cells in which the expression of E6 was regulated by the addition of doxycycline demonstrated clearly that while low levels of E6 protect cells from TNF, high levels sensitize cells. Together, these results demonstrate that virus -host interactions can be complex and that both quantitative and qualitative aspects are important in determining outcome.
AB - High-risk strains of human papillomavirus, including HPV 16, cause human cervical carcinomas, due in part to the activity of their E6 oncogene. E6 interacts with a number of cellular proteins involved in host-initiated apoptotic responses. Paradoxically, literature reports show that E6 can both protect cells from and sensitize cells to tumor necrosis factor (TNF). To examine this apparent contradiction, E6 was transfected into U2OS cells and stable clones were treated with TNF. Intriguingly, clones with a high level of E6 expression displayed an increased sensitivity to TNF by undergoing apoptosis, while those with low expression were resistant. Furthermore, TNF treatment of cells in which the expression of E6 was regulated by the addition of doxycycline demonstrated clearly that while low levels of E6 protect cells from TNF, high levels sensitize cells. Together, these results demonstrate that virus -host interactions can be complex and that both quantitative and qualitative aspects are important in determining outcome.
KW - Apoptosis
KW - Caspase activation
KW - Dose dependence
KW - E6
KW - HPV 16
KW - TNF
UR - https://www.scopus.com/pages/publications/27944454386
UR - https://www.scopus.com/pages/publications/27944454386#tab=citedBy
U2 - 10.1038/sj.cdd.4401678
DO - 10.1038/sj.cdd.4401678
M3 - Article
C2 - 15933739
SN - 1350-9047
VL - 12
SP - 1622
EP - 1635
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 12
ER -