A screening approach with a panel of signal pathway inhibitors was applied to pinpoint which of these pathways has a role in transmitting death signals (Fig 6A).
Next, we examined the signal transducing proteins that transmit death-inducing and death-inhibiting signals, such as ERK, c-jun N-terminal kinase (JNK), and AMP-activated protein kinase (AMPK).
Upon contacting with their corresponding ligands, these receptors are triggered, leading to the recruitment of a different set of adaptor molecules to the death domain and subsequent activation of the signaling cascade, where the major signals transmitted by death receptors such as Fas, TNFR1, TRAILR1, and TRAILR2 result in an apoptotic response mediated by intracellular caspases [ 43– 43].
Secondly, the probability of l output symbols in one window having been transmitted before death of the channel, i.e., Pr(l), can be derived as follows.
The extrinsic apoptosis pathways are triggered by binding of death ligands to transmembrane receptors, so-called death receptors (DRs), thereby transmitting a death signal coming from the outside of the cell.
To discriminate between these possibilities, we established stable knockdown cell lines for FADD and TRADD (shFADD and shTRADD), two important death domain-containing adaptor proteins that transmit death ligand signals from death receptors to caspase 8 (Jin and El-Deiry, 2005).
TRAIL-R3 and TRAIL-R4 are unable to transmit the death signal, since TRAIL-R3 does not have a death domain and TRAIL-R4 has a death domain that is substantially deleted (French and Tschopp, 1999).
In this pathway, activation of caspase-8 following its recruitment to the death-inducing signaling complex is the critical event that transmits the death signal.
The cell survival probability is modeled as the output of an optimization process of transmitting the death signal through a communication channel with a possible environmental and/or inherent distortion.
