Alpha-fetoprotein antagonizes X-linked inhibitor of apoptosis protein anticaspase activity and disrupts XIAP-caspase interaction.

Previous results have shown that the human oncoembryonic protein alpha-fetoprotein (AFP) induces dose-dependent targeting apoptosis in tumor cells, accompanied by cytochrome c release and caspase 3 activation. AFP positively regulates cytochrome c/dATP-mediated apoptosome complex formation in a cell-free system, stimulates release of the active caspases 9 and 3 and displaces cIAP-2 from the apoptosome and from its complex with recombinant caspases 3 and 9 [Semenkova et al. (2003) Eur.

Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation.

Previous results have shown that the oncoembryonic marker alpha-fetoprotein (AFP) is able to induce apoptosis in tumor cells through activation of caspase 3, bypassing Fas-dependent and tumor necrosis factor receptor-dependent signaling. In this study we further investigate the molecular interactions involved in the AFP-mediated signaling of apoptosis. We show that AFP treatment of tumor cells is accompanied by cytosolic translocation of mitochondrial cytochrome c.