Mathematical Structure of RelB Dynamics in the NF-κB Non-Canonical Pathway

Abstract

This study analyzed the non-canonical NF-κB pathway, which controls functions distinct from those of the canonical pathway. Although oscillations of NF-κB have been observed in the non-canonical pathway, a detailed mechanism explaining the observed behavior remains elusive, owing to the different behaviors observed across cell types. This study demonstrated that oscillations cannot be produced by the experimentally observed pathway alone, thereby suggesting the existence of an unknown reaction pathway. Assuming this pathway, it became evident that the oscillatory structure of the non-canonical pathway was caused by stable periodic orbits. In addition, we demonstrated that altering the expression levels of specific proteins reproduced various behaviors. By fitting 14 parameters, excluding those measured in previous studies, this study successfully reproduce nuclear retention (saturation), oscillation, and singular events that had been experimentally confirmed. The analysis also provided a comprehensive understanding of the dynamics of the RelB protein and suggested a potential inhibitory role for the unknown factor. These findings indicate that the unknown factor may be an isoform of IκB, contributing to the regulation of NF-κB signaling. Based on these models, we gained invaluable understanding of biological systems, paving the way for the development of new strategies to manipulate specific biological processes.