Table 5 Analysis of predictions regarding apoptosis in HeLa cells as formulated by Neumann et al

1*

The concentration of anti-CD95 required for the apoptosis induction (the apoptotic threshold), is within the range of 30–100 ng/ml. This range remains the same for CD95 decreased by about 12-fold. The simulation time, which we used to reproduce this prediction, was 60 hours.

2*

The decreased receptor number results in impairment of both CD95- and NF-κB-signaling pathways. To test this prediction, Neumann et al. considered levels of caspases-8 cleavage and IκB-α degradation for the original (solid lines) amount of CD95 and the amount decreased by about 12-fold (dashed lines). The concentration of anti-CD95 was 500 ng/ml.

3*

Along with increasing the concentration of anti-CD95 from 500 ng/ml to 1500 ng/ml, p43/p41 peaks earlier, while there is almost no difference for p43-FLIP.

4

Increased concentrations of cFLIPS inhibit both apoptotic and NF-κB pathways, although p43-FLIP generation is inhibited at a lower threshold than p43/p41 generation.

5*

Increasing the concentration of cFLIPL leads to a steep increase in p43-FLIP generation until it reaches a maximum, after which the curve drops. Lowered levels of cFLIPL result in very little p43-FLIP but almost unchanged levels of p43/p41.

At very high concentrations of cFLIPL no p43-FLIP is generated. This drop-off was not observed experimentally by the authors.

6*

Only an intermediate level of cFLIPL promotes NF-kB activation. Decreased levels of procaspase-8 lead to a significantly lower amount of p43-FLIP and, subsequently, NF-κB. The figures show of logarithmic dependence of the maximal NF-κB concentration on the initial values of procaspase-8 and cFLIPL

7*

High cFLIPL or low procaspase-8 concentrations cause suppression of apoptosis. The figures show the same dependence as considered in the previous prediction, but with caspases-3 instead of NF-κB.