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- Title
IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation.
- Authors
Li, H.-M.; Fujikura, D.; Harada, T.; Uehara, J.; Kawai, T.; Akira, S.; Reed, J. C.; Iwai, A.; Miyazaki, T.
- Abstract
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-β 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.
- Subjects
EPITHELIAL cells; APOPTOSIS; CELL death; CONNECTIVE tissue cells; EXFOLIATIVE cytology
- Publication
Cell Death & Differentiation, 2009, Vol 16, Issue 12, p1615
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/cdd.2009.97