NF-AT

NF-AT or Nuclear Factor of Activated T-cells is a transcription factor that is crucial in the immune response of organisms. It is a protein complex discovered in the cytoplasm of T cells and is activated by the calcineurin pathway.

Structure

NF-AT is a heterodimer composed of a subunit of the Rel (NF-κB) family and a subunit that is activated by calcineurin. The latter subunit is encoded by four different genes: NFAT1, NFAT2, NFAT3, and NFAT4. Each of these genes produces a protein with a Rel homology domain, a calcineurin-binding motif, and a DNA-binding domain.

Function

The primary function of NF-AT is to regulate the transcription of genes that encode cytokines, which are proteins that mediate the immune response. When T cells are activated, the calcium ion concentration in the cytoplasm increases, which activates calcineurin. Calcineurin then dephosphorylates NF-AT, causing it to translocate to the nucleus and bind to specific DNA sequences, thereby initiating the transcription of cytokine genes.

Role in Disease

Abnormalities in the NF-AT pathway have been implicated in several diseases, including autoimmune diseases, cancer, and cardiovascular diseases. For example, overactivation of NF-AT can lead to excessive production of cytokines, which can cause inflammation and tissue damage in autoimmune diseases. On the other hand, underactivation of NF-AT can impair the immune response, making the organism susceptible to infections and cancer.

Therapeutic Potential

Given its crucial role in the immune response, NF-AT is a potential target for therapeutic interventions. Drugs that inhibit the activation of NF-AT, such as cyclosporine and tacrolimus, are already used to prevent organ rejection in transplant patients. However, these drugs have serious side effects, and more specific inhibitors of NF-AT are being developed.

File:NF-AT.png

Structure of the NF-AT protein. Image from Wikimedia Commons.

See Also

• Transcription factor
• Calcineurin
• Cytokines
• Autoimmune diseases
• Cancer
• Cardiovascular diseases

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