AI Article Synopsis
- IAPs (inhibitor-of-apoptosis proteins) help regulate cell death by inhibiting caspases, which are enzymes that facilitate apoptosis.
- Reaper family proteins and Smac/DIABLO can bind to IAPs, preventing them from blocking caspases and promoting apoptosis in both flies and mammals.
- The study identified Omi/HtrA2 as a new protein that binds to the IAP XIAP, has a role in apoptosis, and is released from mitochondria during cell death, suggesting it functions similarly to the Reaper family proteins.
Article Abstract
The inhibitor-of-apoptosis proteins (IAPs) play a critical role in the regulation of apoptosis by binding and inhibiting caspases. Reaper family proteins and Smac/DIABLO use a conserved amino-terminal sequence to bind to IAPs in flies and mammals, respectively, blocking their ability to inhibit caspases and thus promoting apoptosis. Here we have identified the serine protease Omi/HtrA2 as a second mammalian XIAP-binding protein with a Reaper-like motif. This protease autoprocesses to form a protein with amino-terminal homology to Smac/DIABLO and Reaper family proteins. Full-length Omi/HtrA2 is localized to mitochondria but fails to interact with XIAP. Mitochondria also contain processed Omi/HtrA2, which, following apoptotic insult, translocates to the cytosol, where it interacts with XIAP. Overexpression of Omi/HtrA2 sensitizes cells to apoptosis, and its removal by RNA interference reduces cell death. Omi/HtrA2 thus extends the set of mammalian proteins with Reaper-like function that are released from the mitochondria during apoptosis.
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| http://dx.doi.org/10.1074/jbc.M109784200 | DOI Listing |
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