TY - JOUR
T1 - Levels of p53 in Epstein-Barr virus-infected cells determine cell fate
T2 - Apoptosis, cell cycle arrest at the G1/S boundary without apoptosis, cell cycle arrest at the G2/M boundary without apoptosis, or unrestricted proliferation
AU - Chen, Weiping
AU - Huang, Shuang
AU - Cooper, Neil R.
N1 - Funding Information:
This work was supported by U.S. Public Health Service Grants CA52241, AI33241, and EY11431. W.C. was supported by U.S. Public Health Service Training Grant T32 AI07244, and Shuang Huang was supported by ACS Fellowship 2–75-96. This is Scripps Research Institute Manuscript No. 11422-IMM. We thank B. Vogelstein for plasmids, G. Nemerow for helpful advice, and Catalina Hope and Joan Gausepohl for assistance with the manuscript.
PY - 1998/11/25
Y1 - 1998/11/25
N2 - The marked increases in p53 and p21/WAF1 levels that occur during Epstein-Barr virus (EBV) infection and the generation of immortal B lymphoblastoid cell lines (LCL) do not lead to growth arrest or apoptosis, although increasing wild-type (wt) p53 levels in EBV-infected cells by transfection or DNA damage induce these effects. We hypothesized that the concentration of p53 relative to that of LMP1 determines whether EBV-infected B cells undergo growth arrest and apoptosis. Cell cycle arrest and apoptosis were evaluated in LCL expressing varying p53 levels achieved by treating the cells with increasing concentrations of cisplatin, and we supplemented this approach with experiments in EBV-infected Burkitt's lymphoma (BL) cells transfected with a temperature-sensitive (ts) mutant human p53 and studies in LCL infected with recombinant adenoviruses expressing wt and ts mutant p53. Small increases in p53 and p21/WAF1 led to cell cycle arrest at the G2/M boundary, but not to apoptosis; moderate increases resulted in growth arrest at the G1/S boundary, also without apoptosis; and large increases also induced apoptosis. These results confirm the hypothesis and reveal unanticipated complexities in cell cycle regulation by p53.
AB - The marked increases in p53 and p21/WAF1 levels that occur during Epstein-Barr virus (EBV) infection and the generation of immortal B lymphoblastoid cell lines (LCL) do not lead to growth arrest or apoptosis, although increasing wild-type (wt) p53 levels in EBV-infected cells by transfection or DNA damage induce these effects. We hypothesized that the concentration of p53 relative to that of LMP1 determines whether EBV-infected B cells undergo growth arrest and apoptosis. Cell cycle arrest and apoptosis were evaluated in LCL expressing varying p53 levels achieved by treating the cells with increasing concentrations of cisplatin, and we supplemented this approach with experiments in EBV-infected Burkitt's lymphoma (BL) cells transfected with a temperature-sensitive (ts) mutant human p53 and studies in LCL infected with recombinant adenoviruses expressing wt and ts mutant p53. Small increases in p53 and p21/WAF1 led to cell cycle arrest at the G2/M boundary, but not to apoptosis; moderate increases resulted in growth arrest at the G1/S boundary, also without apoptosis; and large increases also induced apoptosis. These results confirm the hypothesis and reveal unanticipated complexities in cell cycle regulation by p53.
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U2 - 10.1006/viro.1998.9431
DO - 10.1006/viro.1998.9431
M3 - Article
C2 - 9837785
AN - SCOPUS:0032567121
SN - 0042-6822
VL - 251
SP - 217
EP - 226
JO - Virology
JF - Virology
IS - 2
ER -