# Analogue information processing in NF-κB gene regulatory system

**Authors:** Pankaj Gautam, Dinesh Kashyap, Debabrata Biswas, Sudipta Kumar Sinha

PMC · DOI: 10.1098/rsos.241487 · Royal Society Open Science · 2025-06-04

## TL;DR

This study explores how the NF-κB system processes information to influence gene expression and cell fate through protein variability and time delays.

## Contribution

The paper introduces a theoretical model showing how protein variability and gene activation delays affect NF-κB dynamics and gene expression.

## Key findings

- Protein variability induces bimodality and influences mean protein numbers.
- Time delays in gene activation lead to oscillations via Hopf bifurcation.
- The study links NF-κB dynamics to downstream gene expression control.

## Abstract

Nuclear factor-κB (NF-κB) participates in various cellular processes to encompass cell fate through differential gene expression, but the underlying molecular mechanism behind this phenomenon is still elusive. Two factors in this process can control the gene expression for determining the cell’s fate: (i) synthesized proteins may have a considerable lifetime and (ii) gene activation may be slow or delayed. To address the first factor, we argue that the NF-κB system experiences cellular variability, often considered the origin of environmental noise for protein production, which influences cellular decisions at the molecular level as they have a considerable lifetime. We employ unified coloured noise approximation to obtain analytical expressions for the protein mean number obtained from our theoretical model and stochastic simulation. We find that these fluctuations influence mean protein numbers and induce bimodality. However, for the second factor, we rely on experimental findings, where the time delay in gene activation plays an essential role in protein production. Our bifurcation analysis demonstrates that the system exhibits saddle-node bifurcations for the instantaneous case, but it experiences the Hopf bifurcation and oscillates between two states in the presence of the time delay. In a nutshell, as NF-κB dynamics influence downstream expression, this study may provide insight into how to adjust parameters to control gene expressions.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790]

## Full-text entities

- **Genes:** NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, GRN [NCBI Gene 101100680], TNF [NCBI Gene 493755], F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, ESR1 [NCBI Gene 552888], ERBB2 [NCBI Gene 751824], Bax [NCBI Gene 493837], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IKKbeta [NCBI Gene 100142682], IRF1 [NCBI Gene 101095633], TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Hes7 [NCBI Gene 101080335]
- **Diseases:** breast cancer (MESH:D001943), SSPD (MESH:D020243), carcinogenic (MESH:D011230), SE (MESH:C535318), immunological diseases (MESH:D007154), carcinogenesis (MESH:D063646), inflammation (MESH:D007249), TE (MESH:C564835), cancer (MESH:D009369), NIB (MESH:D014012)
- **Chemicals:** LPS (MESH:D008070), UCNA (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12133345/full.md

## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12133345/full.md

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Source: https://tomesphere.com/paper/PMC12133345