Nuclear factor NF-kappa-B subunit p65 (p65 (also known as RelA))

Nuclear factor NF-kappa-B subunit p65 (RelA) is a core member of the NF-κB family of transcription factors, which orchestrate the regulation of immune responses, cell survival, inflammation, and many genes involved in cellular stress[2][3][4][5]. The p65 subunit contains a transactivation domain crucial for potent transcriptional activation of target genes, particularly when dimerized with p50. In an inactive state, p65 is sequestered in the cytoplasm in complex with inhibitor IκB proteins. Upon activation by stimuli (e.g., TNFα, pathogens), IκB is degraded, freeing the p65/p50 complex to translocate to the nucleus, bind DNA, and activate gene transcription[1][2][5]. p65 is regulated by various post-translational modifications—such as phosphorylation and acetylation—that fine-tune NF-κB signaling specificity and strength[2][3]. Dysregulation of p65 has been implicated in multiple diseases, especially chronic inflammatory states, cancer, and neurodegenerative disorders, making it an important (but challenging) therapeutic target. (Note: No small molecule exclusively and directly targets p65 clinically, but the listed drugs modulate NF-κB signaling or its upstream effectors[5].)

Other names

RelANF-κB p65Transcription factor p65Nuclear factor NF-κB subunit p65

Inhibition of proteasomal degradation of IκB (prevents p65 nuclear translocation); Suppression of p65 phosphorylation/acetylation (modifies transcriptional activity); Inhibition of upstream kinases (e.g., IKK); Blockade of p65 DNA binding