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Publication : IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation.

First Author  Li HM Year  2009
Journal  Cell Death Differ Volume  16
Issue  12 Pages  1615-21
PubMed ID  19644511 Mgi Jnum  J:169280
Mgi Id  MGI:4940184 Doi  10.1038/cdd.2009.97
Citation  Li HM, et al. (2009) IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation. Cell Death Differ 16(12):1615-21
abstractText  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.
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