tailieunhanh - Báo cáo khoa học: Alpha-fetoprotein antagonizes X-linked inhibitor of apoptosis protein anticaspase activity and disrupts XIAP–caspase interaction

Previous results have shown that the human oncoembryonic proteina-feto-protein (AFP) induces dose-dependent targeting apoptosis in tumor cells, accompanied by cytochromecrelease and caspase 3 activation. AFP posi-tively regulates cytochrome c⁄dATP-mediated apoptosome complex forma-tion 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. J. Biochem. | ỊFEBS Journal Alpha-fetoprotein antagonizes X-linked inhibitor of apoptosis protein anticaspase activity and disrupts XIAP-caspase interaction Elena Dudich1 2 Lidia Semenkova1 2 Igor Dudich1 2 Alexander Denesyuk3 Edward Tatulov2 and Timo Korpela4 1 Institute of ImmunologicalEngineering Lyubuchany Russia 2 JSC BioSistema Moscow Russia 3 Department of Biochemistry and Pharmacy Abo Akademi University Turku Finland 4 Joint Biotechnology Laboratory Turku University Finland Keywords apoptosis apoptosome caspases a-fetoprotein X-linked inhibitor of apoptosis protein Correspondence E. Dudich Institute of Immunological Engineering 142380 Lyubuchany Moscow Region Chekhov District Russia Fax Tel 7 095 996 1555 E-mail elena_dudich@ Received 28 February 2006 revised 3 May 2006 accepted 22 June 2006 doi Previous results have shown that the human oncoembryonic protein a-feto-protein 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. J. Biochem. 270 276-282 . We suggested that AFP might affect the X-linked inhibitor of apoptosis protein XIAP -caspase interaction by blocking binding and activating the apoptotic machinery via abrogation of inhibitory signaling. We show here that AFP cancels XIAP-mediated inhibition of endogenous active caspases in cytosolic lysates of tumor cells as well as XIAP-induced blockage of active recombinant caspase 3 in a reconstituted cell-free system. A direct protein-protein interaction assay showed that AFP physically interacts with XIAP molecule abolishes XIAP-caspase binding and rescues caspase 3 from inhibition. The data suggest that AFP is directly involved in .