The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif
| Autor: | Carol W. Gray, John Savopoulos, Stephen Gschmeissner, Ingram Iaccarino, Caretha L. Creasy, Tencho Tenev, Julian Downward, L. Miguel Martins, Nicholas R. Lemoine, Colin Dingwall, Nicholas F. Totty |
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| Rok vydání: | 2001 |
| Předmět: |
High-Temperature Requirement A Serine Peptidase 2
Programmed cell death Amino Acid Motifs Molecular Sequence Data Apoptosis X-Linked Inhibitor of Apoptosis Protein Biochemistry Mitochondrial Proteins Drosophila Proteins Humans Amino Acid Sequence Molecular Biology Caspase Serine protease Binding Sites biology Reaper fungi Serine Endopeptidases Proteins Cell Biology Molecular biology XIAP Cell biology Mitochondria body regions HtrA serine peptidase 2 biology.protein Peptides |
| Zdroj: | The Journal of biological chemistry. 277(1) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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