VP1 of foot-and-mouth disease virus induces apoptosis via the Akt signaling pathway.
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-3beta 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.
Peng
Jei-Ming
JM
Institutes of Biological Chemistry and Bioagricultural Sciences, Academia Sinica, Taipei 11529, Taiwan.
Liang
Shu-Mei
SM
Liang
Chi-Ming
CM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000472:pathogenicity*; D005814:Genes, Viral; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D036022:Capsid Proteins; D004279:DNA, Viral; D016023:Integrins; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C047981:arginyl-glycyl-aspartic acid; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt