  NF-{\kappa}B is a pleiotropic protein whose nucleo-cytoplasmic trafficking is
tightly regulated by multiple negative feedback loops embedded in the
NF-{\kappa}B signaling network and contributes to diverse gene expression
profiles important in immune cell differentiation, cell apoptosis, and innate
immunity. The intracellular signaling processes and their control mechanisms,
however, are susceptible to both extrinsic and intrinsic noise. In this
article, we present numerical evidence for a universal dynamic behavior of
NF-{\kappa}B, namely oscillatory nucleo-cytoplasmic shuttling, due to the
fundamentally stochastic nature of the NF-{\kappa}B signaling network. We
simulated the effect of extrinsic noise with a deterministic ODE model, using a
statistical ensemble approach, generating many copies of the signaling network
with different kinetic rates sampled from a biologically feasible parameter
space. We modeled the effect of intrinsic noise by simulating the same networks
stochastically using the Gillespie algorithm. The results demonstrate that
extrinsic noise diversifies the shuttling patterns of NF-{\kappa}B response,
whereas intrinsic noise induces oscillatory behavior in many of the otherwise
non-oscillatory patterns. We identify two key model parameters which
significantly affect the NF-{\kappa}B dynamic response and deduce a
two-dimensional phase-diagram of the NF-{\kappa}B response as a function of
these parameters. We conclude that if single-cell experiments are performed, a
rich variety of NF-{\kappa}B response will be observed, even if
population-level experiments, which average response over large numbers of
cells, do not evidence oscillatory behavior.
