Regulation of signal transduction by spatial parameters: a case in NF–κB oscillation

NF-kB is a transcription factor regulating expression of more than 500 genes, and its dysfunction leads to the autoimmune and inflammatory diseases. In malignant cancer cells, NF-kB is constitutively activated. Thus the elucidation of mechanisms for NF-kB regulation is important for the establishment of therapeutic treatment caused by incorrect NF-kB responses. Cytoplasmic NF-kB translocates to the nucleus by the application of extracellular stimuli such as cytokines. Nuclear NF-kB is known to oscillate with the cycle of 1.5–4.5 h, and it is thought that the oscillation pattern regulates the expression profiles of genes. In this review, first we briefly describe regulation mechanisms of NF-kB. Next, published computational simulations on the oscillation of NF-kB are summarised. There are at least 60 reports on the computational simulation and analysis of NF-kB oscillation. Third, the importance of a ‘space’ for the regulation of oscillation pattern of NF-kB is discussed, showing altered oscillation pattern by the change in spatial parameters such as diffusion coefficient, nuclear to cytoplasmic volume ratio (N/C ratio), and transport through nuclear membrane. Finally, simulations in a true intracellular space (TiCS), which is an intracellular 3D space reconstructed in a computer with organelles such as nucleus and mitochondria are discussed.
Source: IET Systems Biology - Category: Biology Source Type: research