Cell Biology

A Complicated Death

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Science  14 Mar 2014:
Vol. 343, Issue 6176, pp. 1178-1179
DOI: 10.1126/science.343.6176.1178-c
CREDIT: S. KALLENBERGER ET AL., SCIENCE SIGNALING 7, 316 (11 MARCH 2014)

Much is known about signaling mechanisms that cause cells to undergo cell death or apoptosis, but it can be hard to know how the many steps play out to determine whether a particular cell lives or dies. Kallenberger et al. therefore undertook a combination of mathematical modeling and experiments on single cells to elucidate how cultured human cells responded to activation of the Fas death receptor. The receptor causes activation of the protease caspase-8, which undergoes multiple cleavage events that control both its activity and substrate preference. Caspase activity in single cells was measured by monitoring fluorescently tagged substrates. This revealed the kinetics of caspase activation and the variability in cell responses. Unexpectedly, a slower rate of cell death in cells exposed to higher concentrations of CD95 ligand was observed. Such a complicated caspase cleavage scheme may enable important characteristics such as switch-like behavior that does not cause cell death in response to low amounts of signal (but shows autoamplification when strongly activated) and a timer mechanism to shut the system down.

Sci. Signal. 7, ra23 (2014).

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