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J. Biol. Chem., Vol. 279, Issue 50, 52168-52174, December 10, 2004

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VP1 of Foot-and-Mouth Disease Virus Induces Apoptosis via the Akt Signaling Pathway^*

Jei-Ming Peng, Shu-Mei Liang¶||, and Chi-Ming Liang¶**

From the Institutes of Biological Chemistry and Bioagricultural Sciences, Academia Sinica, Taipei 11529, Taiwan

Foot-and-mouth disease virus (FMDV) binds to cellular integrins through an RGD motif in its capsid protein, VP1. It is unclear, however, what kind of cellular event(s) are triggered after the binding of VP1 to the cells. In this study, we show that aqueous soluble recombinant DNA-derived VP1 (rVP1) of FMDV induced apoptosis of BHK-21 cells after binding to integrins. In addition, treatment of BHK-21 cells with rVP1 resulted in deactivation of Akt and enhancement of several proapoptotic responses such as dephosphorylation of glycogen synthase kinase-3 and cleavage of procaspase-3, -7, and -9. Additional studies revealed that the rVP1 treatment caused apoptosis of cancer cells, including MCF-7 (a breast carcinoma cell line with a functional deletion of the caspase-3 gene) and PC-3 (a sphingosine 1-phosphate receptor subtype 3-deficient androgen-independent prostate cancer cell line). These results suggest that rVP1 of FMDV may be used selectively as a potent apoptotic agent for human cancer by modulating the Akt signaling pathway and that its effect is not primarily dependent on either activation of procaspase-3 or deactivation of sphingosine 1-phosphate receptor subtype 3.

Received for publication, April 2, 2004 , and in revised form, September 10, 2004.

^* This work was supported by the Biotechnology Research Program of Academia Sinica (to C.-M. L.) and by National Science and Technology Program for Agricultural Biotechnology Grant AS93-AB-IBAS-02 (to S.-M. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Both authors contributed equally to this work.

^|| To whom correspondence may be addressed: Inst. of Bioagricultural Sciences, Academia Sinica, No. 128, Academia Rd., Section 2, Nankang, Taipei 11529, Taiwan. Tel.: 886-2-2652-2870; Fax: 886-2-2651-5120; E-mail: smyang{at}gate.sinica.edu.tw. ** To whom correspondence may be addressed. Tel.: 886-2-2651-8030; Fax: 886-2-2651-8049; E-mail: cmliang{at}gate.sinica.edu.tw.

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