RelA/p65

RelA/p65 is a transcriptionally active subunit of the NF-κB family and functions as a central regulator of inflammatory, immune, cell survival, and stress-response gene expression programs^[1][2]. Upon activation of the canonical NF-κB pathway by pro-inflammatory cytokines, Toll-like receptor signaling, or other cellular stimuli, inhibitory IκB proteins are degraded, allowing RelA-containing NF-κB complexes to translocate into the nucleus and regulate target gene transcription^[3][4]. The predominant NF-κB complex in most cell types is the p50-RelA (p65) heterodimer, which controls the expression of cytokines, chemokines, and survival-associated genes that coordinate innate and adaptive immune responses^[5][6]. Mechanistically, RelA activity is further regulated by post-translational modifications, including phosphorylation, acetylation, methylation, and ubiquitination, which influence its transcriptional output across physiological and pathological conditions^[2]. Dysregulated RelA signaling is strongly associated with chronic inflammation, immune disorders, metabolic disease, and cancer, making this pathway a major focus of translational research and therapeutic development^[1][7][8]. In disease models, genetic or functional disruption of RelA alters inflammatory responses, cell survival, and immune activation, highlighting its essential biological role^[9]. Compared with related NF-κB family members, RelA is distinguished by its prominent role in the canonical pathway and its widespread expression across tissues, whereas c-Rel is enriched in hematopoietic cells and RelB/p52 primarily mediates non-canonical NF-κB signaling^[3][5]. For experimental applications, direct targeting of RelA/p65 and modulation of NF-κB nuclear activity are widely explored strategies for investigating inflammatory mechanisms and evaluating therapeutic interventions^[1].