Figure 6.

An hourglass model of the NFκB signaling network representing the multiple controls within the system that allow differential responses to diverse stimuli. The hourglass shape is characteristic of many robust systems in biology. At the top of the hourglass, the numerous signaling branches and inputs from cross-talk are funneled into the central core regulated by the IKKs. The IKKs integrate these signals to produce a wide-range of cellular responses that are specific to the stimuli. The specificity and diversity are achieved at multiple levels of regulation within the hourglass model (red text). Tissue expression add or subtract inputs to the model depending on which processes are needed in a given cell type. The IKK core regulates responses based on the type, level, and temporal nature of the activation. Negative regulators downstream of the IKK core represent a third level of control.