Transcription factor p65 (RELA) (RELA)

Transcription factor p65 (RELA) is a central component of the NF-kappaB signaling complex, primarily acting as a p65:p50 heterodimer to regulate the expression of genes involved in immunity, inflammation, and cell survival [1, 5]. In resting cells, p65 is sequestered in the cytoplasm by IkappaB inhibitory proteins; however, upon stimulation by proinflammatory cytokines or pathogens, it translocates to the nucleus to initiate transcription [5, 8]. Dysregulation and constitutive activation of p65 are implicated in the pathogenesis of numerous chronic inflammatory conditions and various cancers, where it often promotes tumor cell proliferation and resistance to apoptosis [4, 9, 10]. As a therapeutic target, p65 is addressed through various strategies, including the inhibition of upstream kinases like IKK, the use of proteasome inhibitors to prevent IkappaB degradation, and the development of small molecules that directly block its DNA-binding domain [1, 4, 16]. Despite its high therapeutic potential, the ubiquitous nature of NF-kappaB signaling presents significant challenges, as systemic inhibition can lead to severe side effects such as immunosuppression and hepatotoxicity [1, 10].

Other names

Nuclear factor NF-kappa-B p65 subunitNF-kappa-B p65v-rel avian reticuloendotheliosis viral oncogene homolog ANuclear factor of kappa light polypeptide gene enhancer in B-cells 3p65

Inhibition of IkappaB kinase (IKK) complex activity, prevention of proteasomal degradation of IkappaB proteins, blockade of p65 nuclear translocation, and direct interference with p65 DNA-binding activity or post-translational modifications such as phosphorylation and acetylation.