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NF-κB-dependent Signaling Pathway

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...

NF-kB-dependent Signaling Pathway

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Enzyme-linked Receptors

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...

Enzyme-linked Receptors

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

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Related Experiment Video

Updated: Jun 27, 2026

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.

Seung-Jin Kwag^1,2,3, Jin-Kwon Lee⁴, Seung-Jun Lee^1,2

¹Department of Surgery, Gyeongsang National University College of Medicine, 816-15 Jinju-daero, Jinju 52727, Republic of Korea.

Antioxidants (Basel, Switzerland)

|June 26, 2026

Summary

Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a context-dependent transcriptional platform. Targeting NRF2 partners, not NRF2 itself, offers a more actionable therapeutic strategy, guided by disease context.

Keywords:

BACH1 KEAP1 KEAP1-mutant cancer NRF2 cyclosporin A drug repositioning ferroptosis partner code protein–protein interactions transcriptional coactivators

Related Experiment Videos

Last Updated: Jun 27, 2026

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Area of Science:

Molecular Biology
Cellular Biology
Biochemistry

Background:

Nuclear factor erythroid 2-related factor 2 (NRF2) is traditionally viewed as a stress-response transcription factor regulated by Kelch-like ECH-associated protein 1 (KEAP1).
Emerging evidence indicates NRF2 regulation is more complex, involving parallel E3 ligase systems and coactivator assembly.
The role of NRF2 varies with disease context, potentially promoting metastasis in lung cancer by stabilizing BTB and CNC homology 1 (BACH1).

Purpose of the Study:

To propose a broader framework for understanding NRF2 function beyond the KEAP1-centric model.
To introduce the NRF2 partner-code framework, detailing its modular assembly and regulatory mechanisms.
To identify pharmacologically targetable interfaces within the NRF2 pathway and guide therapeutic strategies.

Main Methods:

Synthesis of existing observations into a novel NRF2 partner-code framework.
Mapping of 22 NRF2 partners onto its Neh-domain architecture.
Stratification of approximately 25 pharmacologically addressable interfaces into four translational tiers.

Main Results:

The NRF2 partner-code framework describes NRF2 as a context-dependent transcriptional platform assembled through four modules: degradation, cytoplasmic scaffold, nuclear coactivator, and DNA/chromatin.
Identification of approximately 25 pharmacologically targetable interfaces associated with NRF2 partners.
Demonstration that disease context dictates the direction of NRF2 modulation, with partners being more actionable targets than NRF2 itself.

Conclusions:

The NRF2 partner-code framework provides a comprehensive view of NRF2 regulation and function.
Targeting NRF2 partners offers a more effective therapeutic approach compared to targeting NRF2 directly.
Future research should focus on disease-specific modulation of NRF2 partners, guided by biomarkers.