RELA proto-oncogene, NF-κB subunit (RELA (commonly referred to as p65))

RELA is a ~65 kDa transcription factor and a key component of the NF-κB complex, most commonly forming a heterodimer with p50. In the cytoplasm, it is sequestered by IκB inhibitors. Upon stimulation by pro-inflammatory signals (e.g., TNF-α, LPS), IκBα is phosphorylated and degraded, releasing RELA/p65 to translocate into the nucleus, where it regulates transcription of genes involved in immunity, inflammation, cell survival, proliferation, and apoptosis. Its activity is tightly regulated by numerous post-translational modifications, which fine-tune DNA binding, coactivator recruitment, and turnover. Constitutive or aberrant activation of RELA is implicated in many cancers by promoting tumor survival and resistance to apoptosis, and in autoimmune and inflammatory diseases by driving pathological gene expression.

Other names

p65NF-κB p65NFKB3NF-kappa B subunit p65RelAv-rel reticuloendotheliosis viral oncogene homolog A (avian)AIF3BL3CMCUNF-κBNF-κB (p65)

Drugs targeting RELA/NF-κB generally act via: - Inhibition of nuclear translocation of the RELA/p65 complex - Blocking IκBα degradation - Direct inhibition of RELA DNA binding - Interfering with post-translational modifications that regulate activity (e.g., phosphorylation, acetylation)