p65/p50 Dimer

The p65/p50 dimer is the most common and functionally important form of the NF-κB transcription factor. It is a heterodimer — a protein complex formed by two different subunits: p65 (RelA) and p50.

🔑 Definition:

The p65/p50 dimer is a protein complex that enters the nucleus and activates gene transcription in response to inflammation, stress, infection, and other cellular signals. It is the classic form of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway.

⚙️ What Are p65 and p50?

Together, they:

• Bind to κB sites in DNA (specific DNA sequences)
• Activate genes involved in inflammation, immunity, cell survival, and stress responses

🔄 Activation Process:

1. In resting cells, the p65/p50 dimer is bound to IκBα in the cytoplasm, keeping it inactive.
2. A stimulus (e.g. TNF-α, LPS, oxidative stress) activates the IKK complex, which phosphorylates IκBα.
3. IκBα is degraded, releasing the p65/p50 dimer.
4. The p65/p50 dimer translocates into the nucleus.
5. It binds to DNA and activates transcription of NF-κB target genes.

🧠 Key Functions of the p65/p50 Dimer:

• Initiates inflammation by turning on genes like:
  • TNF-α
  • IL-1β
  • IL-6
  • COX-2
  • iNOS
• Prevents cell death (anti-apoptotic gene expression)
• Controls immune responses
• Plays a role in cell growth, proliferation, and survival

⚠️ Clinical Importance:

• Chronic activation of the p65/p50 dimer is linked to:
  • Autoimmune diseases (e.g., rheumatoid arthritis)
  • Cancer (promotes tumor survival)
  • Neurodegeneration
  • Chronic inflammation

📌 Summary:

The p65/p50 dimer is the core engine of the NF-κB pathway — driving gene expression that controls inflammation, immunity, and cell survival. Its activity is tightly regulated by IκB proteins and can have both protective and harmful effects, depending on context and duration of activation.