IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation
| Autor: | John C. Reed, Tanenobu Harada, Tadaaki Miyazaki, Daisuke Fujikura, Hong Mei Li, Taro Kawai, Shizou Akira, Atsushi Iwai, Jun Uehara |
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| Rok vydání: | 2009 |
| Předmět: |
Ribosomal Proteins
Cell Caspase 8 Cell Line Mice medicine Animals Humans Anoikis RNA Small Interfering Molecular Biology Adaptor Proteins Signal Transducing DAP3 Gene knockdown Chemistry RNA-Binding Proteins Cell Biology Cell biology Enzyme Activation medicine.anatomical_structure Apoptosis Cell culture Knockout mouse Apoptosis Regulatory Proteins Protein Binding |
| Zdroj: | Cell Death & Differentiation. 16:1615-1621 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-beta promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS-1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation. |
| Databáze: | OpenAIRE |
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