Transcription factor RelA subunit (RELA (commonly known as p65))

Transcription factor RelA subunit (RELA, p65) is a central component of the NF-κB transcription factor family, which comprises five members: NF-κB1 (p105/p50), NF-κB2 (p100/p52), RELA (p65), RELB, and c-REL[1][5][6][7]. The most prevalent and transcriptionally potent form of NF-κB is the RelA/p50 heterodimer, which resides in the cytoplasm complexed with the inhibitor IκBα under resting conditions. After stimulation (e.g., by pro-inflammatory cytokines, pathogens, or stress), IκBα is phosphorylated and degraded via the ubiquitin-proteasome pathway, releasing the RelA/p50 heterodimer, which then translocates into the nucleus to regulate target gene expression[1][5][6]. RelA contains an N-terminal Rel homology domain (RHD) for DNA binding and dimerization, as well as a C-terminal transcriptional activation domain, enabling broad control over inflammatory, immune, and cell survival pathways[1][2][5][6][7]. Dysregulation of RelA activity is implicated in diverse diseases, especially chronic inflammation, cancer, and autoimmune disorders[6][7]. Therapeutic modulation of RelA is being explored with agents that inhibit its activation or DNA binding, but clinical development is challenged by the essential and pleiotropic physiological roles of this transcription factor[7].

Other names

p65RELANF-κB p65 subunitNuclear factor NF-kappa-B p65 subunit

Direct inhibition of RelA DNA binding or activity; Inhibition of IκB kinase (IKK) to prevent IκB degradation, thus sequestering RelA in cytoplasm; Proteasome inhibition to prevent IκB degradation; Modulation of upstream inflammatory signaling to reduce RelA pathway activation