Modulation of p53 by mitogen-activated protein kinase pathways and protein kinase C δ during avian reovirus S1133-induced apoptosis

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• 作者：Ping-Yuan Lin ; Jeng-Woei Lee ; Ming-Huei Liao ; Hsue-Yin Hsu ; Shu-Jun Chiu ; Hung-Jen Liu ; Wen-Ling Shih
• 关键词：ARV S1133 ; p53 ; PKC δ ; MAPK ; Apoptosis
• 刊名：Virology
• 出版年：2009
• 出版时间：15 March 2009
• 年：2009
• 卷：385
• 期：2
• 页码：323-334
• 全文大小：1844 K

文摘

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 δ and p38 and JNK/SAPK pathways, and inhibition of Ras, p38, JNK/SAPK and PKC δ works efficiently against apoptosis. Suppression of p38, JNK/SAPK and PKC δ 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.