title: Regulation of signal transduction by spatial parameters: a case in NF-κB oscillation.
abstract: NF-κB 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-κB is constitutively activated. Thus the elucidation of mechanisms for NF-κB regulation is important for the establishment of therapeutic treatment caused by incorrect NF-κB responses. Cytoplasmic NF-κB translocates to the nucleus by the application of extracellular stimuli such as cytokines. Nuclear NF-κB 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-κB. Next, published computational simulations on the oscillation of NF-κB are summarised. There are at least 60 reports on the computational simulation and analysis of NF-κB oscillation. Third, the importance of a 'space' for the regulation of oscillation pattern of NF-κB 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.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ohshima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sagara
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D016328:NF-kappa B