NF-κB Signaling Pathway – Functions, Disease Implications and Biomarker Analysis

Q: What is the role of the NF-κB signaling pathway?

The NF-κB signaling pathway regulates inflammation, immune responses, cell survival, and stress adaptation by controlling the expression of a wide range of target genes.

Q: What activates NF-κB signaling?

NF-κB signaling is activated by pro-inflammatory cytokines, microbial products, oxidative stress, and cellular damage signals.

Q: Which diseases are associated with NF-κB dysregulation?

Dysregulation of NF-κB signaling is associated with chronic inflammatory diseases, cancer, cardiovascular disorders, and neurodegenerative diseases.

Q: What is the difference between canonical and non-canonical NF-κB signaling?

The canonical NF-κB pathway mediates rapid inflammatory and innate immune responses, whereas the non-canonical pathway regulates adaptive immunity and lymphoid organ development.

Q: How can NF-κB signaling pathway activity be analyzed?

NF-κB signaling pathway activity can be analyzed by measuring the expression of pathway regulators and downstream target genes using targeted gene expression approaches such as qPCR pathway arrays.

What is the NF-κB signaling pathway?

The NF-κB signaling pathway (nuclear factor kappa-light-chain-enhancer of activated B cells pathway) is a central regulatory pathway controlling immune response, inflammation, cell survival, and stress adaptation.

NF-κB signaling is activated by a wide range of stimuli, including pro-inflammatory cytokines, microbial infections, oxidative stress, and cellular damage. Once activated, NF-κB transcription factors translocate to the nucleus and regulate the expression of genes involved in immune defense, inflammation, apoptosis, and cell proliferation.

Dysregulation of NF-κB signaling is strongly associated with chronic inflammatory diseases, cancer, cardiovascular disorders, and neurodegenerative conditions, making it one of the most intensively studied signaling pathways in biomedical research.

NF-κB pathway activity can be efficiently assessed through targeted gene expression analysis of pathway regulators and downstream transcriptional targets.

NF-κB signaling pathway biomarker list
View the genes and molecular targets included in our NF-κB pathway qPCR arrays.

Schematic diagram of the canonical and non-canonical Nuclear factor kappa B (NF-κB) signaling pathways.

Key takeaways

Master regulator of inflammation and immune responses
Rapid signal transmission from cytoplasm to nucleus
Operates through canonical and non-canonical pathways
Strongly implicated in cancer and chronic inflammatory diseases
Highly suitable for biomarker discovery and gene expression profiling

Core components of the NF-κB pathway

NF-κB transcription factor dimers

NF-κB exists as homo- or heterodimers composed of RelA (p65), RelB, c-Rel, p50, and p52 subunits.

IκB inhibitory proteins

IκB proteins sequester NF-κB dimers in the cytoplasm and prevent nuclear translocation under resting conditions.

IKK complex

The IκB kinase (IKK) complex, composed of IKKα, IKKβ, and IKKγ/NEMO, phosphorylates IκB proteins, targeting them for proteasomal degradation.

Upon IκB degradation, NF-κB dimers translocate to the nucleus and activate gene transcription.

Canonical and non-canonical NF-κB activation pathways

Canonical pathway

Triggered by TNF-α, IL-1, microbial products, and stress signals
Involves IKKβ-mediated IκB degradation
Activates RelA/p50 dimers
Regulates acute inflammation and innate immunity

Non-canonical pathway

Activated by specific stimuli such as BAFF, CD40, and lymphotoxin-β
Involves processing of p100 to p52
Activates RelB/p52 dimers
Controls lymphoid organogenesis and adaptive immune responses

Biological functions of NF-κB signaling

NF-κB signaling regulates essential cellular and physiological processes:

Inflammation: Induction of cytokines, chemokines, and inflammatory mediators.

Immune responses: Regulation of innate and adaptive immunity.

Cell survival and apoptosis: Induction of anti-apoptotic gene programs.

Cell proliferation: Control of growth-related transcriptional networks.

Stress and damage responses: Adaptation to oxidative stress and cellular injury.

Pathway cross-talk and signal integration

NF-κB signaling interacts extensively with other signaling networks:

- MAPK signaling – coordination of inflammatory gene expression
- PI3K-AKT signaling – promotion of cell survival under stress
- Wnt/β-catenin signaling – modulation of tumor progression and immune evasion

This cross-talk adds regulatory complexity and expands the range of NF-κB-dependent biological outcomes.

Therapeutic targeting of NF-κB signaling

Given its central role in disease, NF-κB is a major therapeutic target:

Small-molecule NF-κB and IKK inhibitors in clinical development
Anti-inflammatory strategies targeting upstream activators
Combination therapies in oncology and chronic inflammatory diseases

NF-κB signaling dysregulation and disease

Chronic inflammatory diseases

Persistent NF-κB activation contributes to:

Rheumatoid arthritis
Inflammatory bowel disease
Asthma

Cancer

Constitutive NF-κB signaling promotes:

Tumor cell survival
Angiogenesis
Metastasis
Resistance to chemotherapy

Cardiovascular and neurodegenerative disorders

NF-κB dysregulation is implicated in:

Atherosclerosis and heart failure
Alzheimer’s and Parkinson’s diseases

Why study the NF-κB signaling pathway with AnyGenes?

At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® designed for NF-κB pathway analysis and biomarker discovery. Our solutions enable researchers to:

Quantify NF-κB-dependent gene expression signatures
Analyze upstream regulators and downstream transcriptional targets
Study pathway cross-talk with MAPK, PI3K-AKT, and JAK-STAT
Generate robust, reproducible, and publication-ready data

NF-κB signaling pathway biomarker analysis with AnyGenes®

What can be analyzed?

NF-κB subunits and regulatory components
Inflammatory cytokines and chemokines
Cell survival and apoptosis-related genes
Disease-associated NF-κB biomarkers

Available solutions

Pre-designed NF-κB Pathway qPCR Arrays
Fully customizable SignArrays®
Expert support for experimental design and data interpretation

Customize your own signaling pathways (SignArrays^®) with the factors of your choice!
Simply download and complete our Personalized SignArrays^® information file and send it at [email protected] to get started on your project.

Frequently asked questions

What is the role of the NF-κB signaling pathway?

NF-κB signaling regulates inflammation, immune responses, cell survival, and stress adaptation by controlling the expression of numerous target genes.

What activates NF-κB signaling?

NF-κB is activated by cytokines, microbial products, oxidative stress, and cellular damage signals.

Which diseases are associated with NF-KB pathway dysregulation?

NF-κB dysregulation is linked to chronic inflammatory diseases, cancer, cardiovascular disorders, and neurodegenerative diseases.

What is the difference between canonical and non-canonical NF-κB signaling?

The canonical pathway mediates rapid inflammatory responses, while the non-canonical pathway regulates adaptive immunity and lymphoid development.

How can NF-κB pathway activity be analyzed?

NF-κB activity can be analyzed by measuring the expression of pathway regulators and downstream target genes using targeted qPCR pathway arrays.

Wang Y, et al. NF-κB signaling in skin aging. Mech Ageing Dev. (2019);184:111160.
Soleimani A, et al. Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer. Gene. (2020);726:144132.
Ramadass V, et al. Small Molecule NF-κB Pathway Inhibitors in Clinic. Int J Mol Sci. (2020);21(14):5164.
Singh S, & Singh TG. Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach. Curr Neuropharmacol. (2020);18(10):918-935

NF-KB signaling pathway biomarker list

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human NFKB pathway

Signaling Pathways	Product ref	Informations
NFKB Signaling Pathway	NFKB1H1	List infos

Species : Mus musculus (mouse)

Mouse NFKB pathway

Signaling Pathways	Product ref	Informations
NFKB Signaling Pathway	NFKB1M1	List infos

Species : Rattus norvegicus (rat)

Rat NFKB pathway

Signaling Pathways	Product ref	Informations
NFKB Signaling Pathway	*******	List In progress...

Species : Sus Scrofa (Pig)

Pig NF-κB Signaling

Signaling Pathways	Product ref	Informations
NFKB Signaling Pathway	*******	List In progress...

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