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Avian Reovirus activates a novel proapoptotic signal by linking Src to p53

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Abstract

We have previously shown that avian reovirus (ARV) S1133 and its structural protein σC cause apoptosis in cultured Vero cells through an unknown intracellular signaling pathway. This work investigates how ARV S1133 induces proapoptotic signals. Upon ARV S1133 infection and subsequent apoptosis, levels of p53 mRNA and protein, and p53 serine-46 and serine-392 phosphorylation increased. In addition, p53-driven reporter activity and levels of the p53-induced apoptotic protein bax were increased, and Src tyrosine-418 phosphorylation was elevated. UV-inactivated virus failed to activate Src, p53 or induce apoptosis. Over-expression of dominant negative p53, or treatment with tyrosine kinase inhibitor genistein protected cells from ARV S1133-induced apoptosis. Inhibition of Src by over-expression of C-terminal Src kinase (Csk) or treatment with Src family tyrosine kinase inhibitor SU-6656 diminished the ARV S1133-induced p53 expression, activation, and apoptosis. Over-expression of σC resulted in the upregulation of p53, p53 serine-46 phosphorylation, p53-driven reporter activity and accumulation of bax. σC expression during ARV S1133 infection was concomitant with the onset of apoptosis. These studies provide strong evidence that the viral gene expression is required for ARV S1133 to initiate a proapoptotic signal via Src to p53. In addition, σC was able to utilize a p53-dependent pathway to elicit apoptosis.

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Authors and Affiliations

  1. Graduate Institute and Department of Life Science, Tzu-Chi University, 701, Sec. 3, Chung-Yang Rd., Hualien, Taiwan, 970

    Lin Ping-Yuan, Hsu Hsue-Yin, Lee Jeng-Woei & Shih Wen-Ling

  2. Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan

    Liu Hung-Jen & Yu Feng-Ling

  3. Department of Laboratory Medicine and Biotechnology, Tzu-Chi University, Hualien, Taiwan

    Lai Meng-Jiun

  4. Department of Nursing, Tzu-Hui Institute of Technology, Pingtung, Taiwan

    Yu Feng-Ling

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  1. Lin Ping-Yuan
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Correspondence to Shih Wen-Ling.

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Ping-Yuan, L., Hung-Jen, L., Meng-Jiun, L. et al. Avian Reovirus activates a novel proapoptotic signal by linking Src to p53. Apoptosis 11, 2179–2193 (2006). https://doi.org/10.1007/s10495-006-0291-6

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