Nuclear factor kappa B p65 subunit (RELA)

The Nuclear factor kappa B p65 subunit (RELA) is one of five major NF-κB family members, forming the most abundant functional heterodimer with p50. It is primarily regulated by retention in the cytoplasm via IκB proteins. Upon pro-inflammatory or immune stimulation (e.g., by TNFα), IκB is phosphorylated by the IKK complex and degraded, permitting NF-κB p65 translocation to the nucleus, where it activates transcription of genes involved in immunity, inflammation, cell proliferation, and survival. Phosphorylation of p65 at specific residues (such as Ser276, Ser536) is an essential step for maximal transcriptional activity, influencing interaction with transcriptional coactivators and DNA. NF-κB p65 plays critical roles in inflammatory diseases, cancer, neurodegeneration, and cardiovascular disease. It is a key drug discovery target, though direct inhibition remains challenging given its central physiological roles.

Other names

NF-κB p65 subunitTranscription factor p65RELANFKB3v-rel avian reticuloendotheliosis viral oncogene homolog A

Inhibition of IκB kinase (IKK) activity blocks IκB phosphorylation, preventing NF-κB p65 activation and nuclear translocation. Direct inhibition of p65 DNA binding (experimental). Suppression of upstream signaling, leading to decreased phosphorylation or expression of p65.