dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD.
Apoptotic cell death occurs through activation of procaspases, the precursors of a group of aspartate-specific cysteine proteases known as caspases. Procaspase activation is mediated by death adapter proteins such as the mammalian proteins FADD and Apaf-1 and the Caenorhabditis elegans protein CED-4. These adapters bind to procaspases and facilitate oligomerization and subsequent auto-proteolytic processing of the zymogens. Here we report cloning and characterization of dFADD, a FADD homologue in Drosophila. dFADD contains a death domain that is highly homologous to the FADD death domain, and it also shares a novel domain with a Drosophila caspase DREDD, which we call death-inducing domain. dFADD binds to DREDD through the death-inducing domain and enhances the cell death activity and proteolytic processing of DREDD. dFADD and DREDD are stabilized by their interaction. The structural and functional similarities between dFADD and FADD suggest the existence of a FADD-like apoptosis pathway in Drosophila.
Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D020169:Caspases / Q000737:chemistry*; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000201:enzymology; D029721:Drosophila Proteins; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D002352:Carrier Proteins; D029721:Drosophila Proteins; D004792:Enzyme Precursors; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D011506:Proteins; C400550:dark protein, Drosophila; D020169:Caspases