DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9 |
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Authors: | Ekert P G Silke J Hawkins C J Verhagen A M Vaux D L |
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Institution: | The Walter and Eliza Hall Institute, The Royal Melbourne Hospital, Victoria 3050, Australia. |
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Abstract: | MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here, we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis. |
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Keywords: | apoptosis IAPs DIABLO caspases BIR |
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