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Sci. Signal., 18 December 2012
Vol. 5, Issue 255, p. ra93
[DOI: 10.1126/scisignal.2003558]


Editor's Summary

FLIPping Multiple Death Signals Off
The gene c-Flip, which encodes the antiapoptotic protein c-FLIP, is expressed in response to nuclear factor {kappa}B (NF-{kappa}B) activation. NF-{kappa}B–mediated protection of the intestine and liver from proapoptotic signaling is important for tissue maintenance (homeostasis). Avoiding the embryonic lethality caused by complete knockout of c-Flip in mice, Piao et al. selectively deleted c-Flip in intestinal epithelial cells (IECs) or hepatocytes. Whereas c-FLIP–deficient IECs exhibited tumor necrosis factor (TNF)–dependent apoptosis and programmed necrosis, a cell death process morphologically and mechanistically distinct from that of apoptosis, leading to perinatal death of the mice, c-FLIP–deficient hepatocytes exhibited apoptosis and programmed necrosis, and mice died in a TNF-independent manner. Induced loss of c-FLIP in hepatocytes in adult mice led to lethal hepatitis, which was prevented by blocking multiple proinflammatory factors that trigger apoptosis. Together, these data show that c-FLIP blocks both apoptosis and programmed necrosis to maintain tissue homeostasis and suggest that targeting both cell death pathways may be effective in treating certain viral infections in which c-FLIP abundance is reduced.

Citation: X. Piao, S. Komazawa-Sakon, T. Nishina, M. Koike, J.-H. Piao, H. Ehlken, H. Kurihara, M. Hara, N. Van Rooijen, G. Schütz, M. Ohmuraya, Y. Uchiyama, H. Yagita, K. Okumura, Y.-W. He, H. Nakano, c-FLIP Maintains Tissue Homeostasis by Preventing Apoptosis and Programmed Necrosis. Sci. Signal. 5, ra93 (2012).

Read the Full Text

The FLIP Side of Life.
J. Silke and A. Strasser (2013)
Science Signaling 6, pe2
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