XIAP Regulates DNA Damage-induced Apoptosis Downstream of Caspase-9 Cleavage
| Autor: | Verena Biedermann, Jian Ren, Kazuya Endo, Donald Kufe, Eiji Oki, Rakesh Datta |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Programmed cell death
DNA damage Apoptosis Cytochrome c Group X-Linked Inhibitor of Apoptosis Protein DNA Fragmentation Transfection Cleavage (embryo) Models Biological Biochemistry chemistry.chemical_compound Humans Molecular Biology Caspase-9 Caspase 8 Enzyme Precursors biology Caspase 3 Cytarabine Proteins U937 Cells Cell Biology Caspase Inhibitors Precipitin Tests Molecular biology Caspase 9 Peptide Fragments Mitochondria XIAP Enzyme Activation HtrA serine peptidase 2 chemistry Caspases biology.protein Protein Processing Post-Translational DNA DNA Damage Mutagens Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 275:31733-31738 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m910231199 |
| Popis: | The IAP (inhibitor ofapoptosis) family of anti-apoptotic proteins regulates programmed cell death. Of the six known human IAP-related proteins, XIAP is the most potent inhibitor. To study the mechanistic effects of XIAP on DNA damage-induced apoptosis, we prepared U-937 cells that stably overexpress XIAP. The results demonstrate that XIAP inhibits apoptosis induced by 1-[β-d-arabinofuranosyl]cytosine (ara-C) and other genotoxic agents. XIAP had no detectable effect on ara-C-induced release of mitochondrial cytochrome c and attenuated cleavage of procaspase-9. In addition, we show that ara-C induces the association of XIAP with the cleaved fragments of caspase-9 and thereby inhibition of caspase-9 activity. The results also demonstrate that ara-C induces cleavage of procaspase-3 by a caspase-8-dependent mechanism and that XIAP inhibits caspase-3 activity. These results demonstrate that XIAP functions downstream of procaspase-9 cleavage as an inhibitor of both proteolytically processed caspase-9 and -3 in the cellular response to genotoxic stress. |
| Databáze: | OpenAIRE |
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