Transcription factor p65 (RELA) (p65)

Transcription factor p65, also known as RELA, is a pivotal member of the NF-kappa-B (NF-κB) family, serving as a primary mediator of the canonical NF-κB signaling pathway [1, 2]. Under resting conditions, p65 is held in the cytoplasm in an inactive state by inhibitory proteins known as IκBs [3]. Upon stimulation by pro-inflammatory cytokines, growth factors, or pathogen-associated molecular patterns, the IκB kinase (IKK) complex phosphorylates IκB, leading to its degradation and the subsequent nuclear translocation of p65 [1, 3]. Once inside the nucleus, p65 binds to specific κB sites on DNA to induce the expression of genes involved in the immune response, cell survival, and inflammation [1, 3]. Aberrant p65 activity and persistent nuclear translocation are frequently observed in chronic inflammatory conditions, autoimmune disorders, and various malignancies, where they drive disease progression and therapeutic resistance [4]. Pharmacological targeting of p65 translocation includes the use of proteasome inhibitors, IKK inhibitors, and small molecules that directly block its entry into the nucleus or its DNA-binding capacity [4, 5]. Because p65 is essential for normal physiological processes and host defense, its inhibition poses significant challenges regarding systemic toxicity and immunosuppression [3, 5]. Current research focuses on developing more selective inhibitors that can modulate p65 activity without completely abolishing its protective functions [4].

Other names

RELANFKB3Nuclear factor NF-kappa-B p65 subunitv-rel avian reticuloendotheliosis viral oncogene homolog A

Inhibition of IκB kinase (IKK) complex to prevent IκB degradation, direct inhibition of p65 nuclear translocation, or blockade of p65 DNA binding.