The Apoptotic Signaling Network Dynamically Interprets the Outputs of Individual Signaling Pathways in an Early Analog and Late Digital Manner

Changes in cell behavior are determined by a network of proteins that actively transmits signaling information (Irish et al., 2004; Jordan et al., 2000; Pawson, 2004). Modulation of total levels of key proteins, as well as their posttranslational states and enzymatic activities, could all potentially act as “molecular signals” that are monitored and interpreted. To understand how complex signal-transduction events control cell responses, these molecular signals must be measured dynamically and then mapped to downstream changes in cell outcome (Gaudet et al., 2005; Janes et al., 2005). Such approaches can accurately predict diverse cellular responses and suggest how molecular information is organized and propagated within the cell (Miller-Jensen et al., 2007).

One crucial cell decision is whether to die or to survive (Green and Evan, 2002; Kyriakis, 2001; Tran et al., 2004). Apoptosis is a common mechanism of cell death in response to many intrinsic and extrinsic cytotoxic cues such as cytokines and DNA damage (Strasser et al., 2000; Zhou and Elledge, 2000). Neighboring cells can also directly induce apoptosis in a target cell by secreting prodeath factors. Although cell death is important for normal development and tissue homeostasis, it is irreversible, requiring apoptosis to be tightly controlled. Deregulated apoptosis is known to be involved in many human diseases such as cancer (Rudin and Thompson, 1997; Vaux, 1993).