NF-κB

Definition

NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) is a protein complex that plays a crucial role in regulating immune response, cell survival, and inflammation. This transcription factor is activated in response to various stimuli, including cytokines and stress signals, and is essential for mediating the cellular response to these signals by controlling the expression of specific genes.

5 Must Know Facts For Your Next Test

1. NF-κB is usually found in the cytoplasm in an inactive form bound to IκB proteins, which keep it from entering the nucleus.
2. Upon activation by stimuli such as inflammatory cytokines or stress, IκB proteins are degraded, allowing NF-κB to translocate to the nucleus.
3. Once in the nucleus, NF-κB binds to specific promoter regions of target genes, initiating their transcription, which includes genes involved in inflammation and immune responses.
4. Dysregulation of NF-κB activity is linked to various diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions.
5. The NF-κB signaling pathway is tightly regulated by multiple mechanisms to ensure a balanced response to cellular stress and inflammation.

Review Questions

• How does NF-κB become activated and what is its role in gene expression?
  • NF-κB becomes activated when external signals like cytokines trigger the degradation of IκB proteins that normally keep it sequestered in the cytoplasm. Once released, NF-κB translocates to the nucleus where it binds to specific DNA sequences to promote the transcription of genes involved in inflammation and immune response. This activation is crucial for orchestrating a cellular response during stress or infection.
• Discuss the implications of NF-κB dysregulation in disease processes.
  • Dysregulation of NF-κB can lead to inappropriate activation or repression of target genes, contributing to various diseases. In cancer, persistent activation can promote cell proliferation and survival, leading to tumor growth. In autoimmune diseases, unchecked NF-κB activity can drive excessive inflammatory responses. Thus, understanding NF-κB's regulation is vital for developing targeted therapies.
• Evaluate the potential therapeutic strategies targeting NF-κB signaling pathways for treating inflammatory diseases.
  • Therapeutic strategies targeting NF-κB signaling may involve the use of inhibitors that block IκB degradation or prevent NF-κB from entering the nucleus. These approaches could reduce excessive inflammation in conditions like rheumatoid arthritis or inflammatory bowel disease. Furthermore, compounds that modulate upstream signaling pathways could also be explored to restore normal regulatory mechanisms. By fine-tuning NF-κB activity, treatments could effectively mitigate disease symptoms while minimizing side effects.

Related terms

Cytokines: Small signaling proteins released by cells that affect the behavior of other cells, especially in immune responses.

Transcription Factors: Proteins that bind to specific DNA sequences to regulate the transcription of genes, influencing cell function and identity.

IκB Proteins: Inhibitors of NF-κB that sequester the NF-κB complex in the cytoplasm, preventing its action until signals lead to their degradation.