Modulation of p53 by mitogen-activated protein kinase pathways and protein kinase C delta during avian reovirus S1133-induced apoptosis.
ARV S1133 infection caused apoptosis in vivo and in vitro; however, the intracellular signaling pathways have not been fully delineated. We have previously demonstrated that ARV S1133 activates proapoptotic signaling from Src to p53, and further investigated how ARV S1133 modulates p53. We found that ARV S1133 forms syncytia and induces apoptosis in CEF, DF1 and Vero cells with different kinetics. Enhancement of p53 phosphorylation and DNA-binding capacity to bax and bad promoters was found in this study to increase bax and bad expression in ARV S1133-infected cells. ARV S1133 activates PKC delta and p38 and JNK/SAPK pathways, and inhibition of Ras, p38, JNK/SAPK and PKC delta works efficiently against apoptosis. Suppression of p38, JNK/SAPK and PKC delta selectively abolished ARV S1133-mediated p53 phosphorylation; moreover, inhibition of Src did not affect ARV S1133-induced p38 and JNK/SAPK activation, whereas blocking of Ras resulted in a reduction in the activities of p38 and JNK/SAPK.
Lin
Ping-Yuan
PY
Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan.
Lee
Jeng-Woei
JW
Liao
Ming-Huei
MH
Hsu
Hsue-Yin
HY
Chiu
Shu-Jun
SJ
Liu
Hung-Jen
HJ
Shih
Wen-Ling
WL
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D030101:Orthoreovirus, Avian / Q000502:physiology*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014709:Vero Cells; D018631:ras Proteins / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins