Apoptosis induced by human Fas-associated factor 1, hFAF1, requires its ubiquitin homologous domain, but not the Fas-binding domain.
FAF1 is a Fas-binding protein without typical death domain. Instead, FAF1 has several domains found in proteins of ubiquitination pathway. Transient overexpression of hFAF1 in BOSC23 cells caused membrane blebbing and cell body condensation which were characteristics of apoptosis. Subsequent analysis revealed that overexpression of hFAF1 induced nuclear condensation, appearance of phosphatidylserines in the outer leaflet of the cellular membrane, and caspase 3 activation. The apoptotic potential of hFAF1 required downstream ubiquitin homologous domain (UB2) and adjacent nuclear localization signal but not the Fas-binding domain. Our data showed that mere intrinsic overexpression of hFAF1 initiated apoptosis in the absence of any extrinsic death signal in BOSC23 cells.
Ryu
S W
SW
Research Center for Biomedicinal Resources and Division of Life Science, PaiChai University, 439-6 Doma-dong, Seo-gu, Taejon, 302-735, South Korea.
Kim
E
E
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D019913:Nuclear Localization Signals; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014162:Transfection; D014452:Ubiquitins / Q000737:chemistry*; D019014:fas Receptor / Q000737:chemistry*
D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; C490780:FAF1 protein, human; D005456:Fluorescent Dyes; D019913:Nuclear Localization Signals; D014452:Ubiquitins; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases