Nuclear factor NF-kappa-B p65 subunit (RELA) (RELA)

The Nuclear factor NF-kappa-B p65 subunit, also known as RELA, is a critical transcription factor that mediates the canonical NF-kappa-B signaling pathway (UniProt P22301). It exists as a heterodimer, most commonly with p50, and is normally sequestered in the cytoplasm by IkappaB inhibitory proteins. Upon activation by stimuli such as TNF-alpha or Toll-like receptor ligands, the IkappaB kinase (IKK) complex phosphorylates IkappaB, leading to its proteasomal degradation and the subsequent translocation of p65 to the nucleus (PubMed: 24353513). Once in the nucleus, p65 binds to specific DNA sequences to regulate the expression of genes involved in inflammation, cell survival, and the immune response. Aberrant p65 activity is a hallmark of many chronic inflammatory conditions and malignancies, where it contributes to tumor progression and chemoresistance (PubMed: 30524415). Consequently, the p65 pathway is a major focus for drug development, with therapies like proteasome inhibitors and corticosteroids widely used to modulate its activity, although systemic inhibition poses risks of significant immunosuppression.

Other names

p65RELANFKB3Transcription factor p65Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3

Inhibition of IkappaB kinase (IKK) complex, prevention of IkappaB degradation via proteasome inhibition, or direct interference with nuclear translocation and DNA binding.